benzoylecgonine and Substance-Related-Disorders

Topics: Animals; Cocaine; Drug Interactions; Ethanol; Humans; Oxidation-Reduction; Rats; Substance-Related Disorders

Topics: Cocaine; Humans; Narcotics; Substance Abuse Detection; Substance-Related Disorders; Urinalysis

Cocaine is considered a superb anesthetic for many otolaryngologic procedures and has been shown to be positive in the urine of patients for up to 72 hours after surgery with a standard radioimmunoassay test. The standard cutoff for drug screening of benzoylecgonine, the main urine metabolite of cocaine, has been 300 ng/ml. However, the new threshold value in many laboratories is now 150 ng/ml. In review of the literature, no study has been performed that quantitates the actual level of the urine cocaine metabolite after a routine otolaryngologic procedure in both physicians and their patients with the gold standard for urine testing, gas chromatography. This study documents the quantitative level of the urine cocaine metabolite in patients and reveals that there are metabolite levels present in physicians during a single exposure, although they are below the current cutoff level that will be picked up on current screening assays. Evidence has also been presented demonstrating a cumulative effect on the benzoylecgonine levels in physicians who clinically use cocaine anesthesia more frequently; these levels can be above the cutoff level on current screening assays.

Topics: Administration, Intranasal; Anesthetics, Local; Chromatography, Gas; Cocaine; Gas Chromatography-Mass Spectrometry; Gloves, Surgical; Humans; Masks; Mass Screening; Narcotics; Occupational Exposure; Otorhinolaryngologic Diseases; Patients; Physicians; Substance-Related Disorders; Time Factors

Detection of benzyolecgonine, the major metabolite of cocaine, in the urinalysis conducted on the first day of an inpatient heroin detoxification treatment program was studied as a predictor of discharge against medical advice (AMA). With this aim, we conducted a chart-review procedure of 275 heroin dependents (DSM-III-R) who received methadone or dextropropoxyphene chlorhydrate to treat Opioid Withdrawal Syndrome. Data were analyzed following a case-control design. The 49 (17.8%) patients who did not complete the treatment due to discharged AMA were characterized by having achieved total heroin abstinence during fewer months from the time they began consumption of this substance to the time of hospitalization (p = .001). Moreover, those patients who requested discharge AMA were characterized by more frequent detection of benzoylecgonine in their urine on the day of admission (p = .004). The value of the odds ratio of this association was 3.81 (95% CI; 1.30 to 11.04). Lastly, noncompleters due to discharge AMA were more likely to be single than ever married (p = .037). The logistic regression model confirmed that there is a significant relationship between an AMA event and the presence of benzoylecgonine in urine upon beginning detoxification and to a shorter duration of the period of total heroin abstinence. In the discussion, the influence that recent interruption of cocaine consumption has on the decision to drop out of a detoxification program AMA is considered.

Topics: Analgesics, Opioid; Analysis of Variance; Antiemetics; Cocaine; Counseling; Dextropropoxyphene; Diazepam; Female; Heroin Dependence; Humans; Male; Methadone; Patient Discharge; Patient Dropouts; Regression Analysis; Substance Abuse Treatment Centers; Substance-Related Disorders; Time Factors

Psychometric data are presented which examine the validity of using the concentration of benzoylecgonine in urine, a major metabolite of cocaine, as a measure of drug use, in studies of drug abuse treatments. In such research the standard biological indicator of drug use is usually a qualitative urine drug test, which merely indicates the presence or absence of a drug or its metabolite. A quantitative (i.e. continuous) outcome measure, such as the concentration of a drug or its metabolite in a biological fluid, has substantially more statistical power than a dichotomous measure and should, therefore, prove a more sensitive measure of drug use when viewed from a measurement perspective. Data from two placebo-controlled clinical trials of fluoxetine as an adjunct to treatment for cocaine abuse are analyzed to address this issue. Results indicate that urine benzoylecgonine level is closely related to self-reports of drug use and is independent of levels of anxiety, depression and hopelessness.

Topics: Adult; Biomarkers; Cocaine; Double-Blind Method; Female; Humans; Male; Narcotics; Substance Abuse Detection; Substance-Related Disorders

Sixty-five cocaine-dependent subjects were enrolled into a 10-week randomized, double-blind study to determine the safety and efficacy of the serotonin-2 receptor antagonist, ritanserin (10 mg/day), in reducing cocaine consumption and craving. All subjects also participated in a structured intensive outpatient psychosocial program. Seventy-three percent of the participants completed the treatment program and follow-up. Subjects experienced a significant reduction in craving: 66.4% and 32.5% for the placebo and ritanserin groups, respectively. These reductions in craving were not paralleled by substantial decreases in cocaine use. Self-reported cocaine use was less frequent in the placebo group; paradoxically, blood levels of its metabolite, benzoylecgonine, were also higher although insignificantly so. Generally, ritanserin was well tolerated but significantly prolonged the QTc interval on the electrocardiogram. This outpatient program is effective at maintaining cocaine-dependent individuals in treatment and reducing craving. Ritanserin (10 mg/day) is not an efficacious adjunct to psychosocial treatment for cocaine dependence.

Topics: Adult; Cocaine; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Ritanserin; Serotonin Antagonists; Severity of Illness Index; Substance-Related Disorders

We report on a double-blind, placebo-controlled study of carbamazepine (CBZ) treatment for cocaine dependence. A previously reported uncontrolled study found CBZ to be a beneficial pharmacotherapy for cocaine dependence. Statistical analyses were performed on data from 82 subjects who were randomized to 10 weeks' treatment with either CBZ, titrated to 4-12 micrograms/ml, (n = 37) or placebo (n = 45). The two treatment groups did not differ for primary outcome measures of retention time in treatment, urine samples positive for cocaine metabolite, subject reported desire for cocaine or for subject reported side-effects. CBZ was not an effective treatment in this study.

Topics: Adult; Anticonvulsants; Carbamazepine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Kindling, Neurologic; Male; Middle Aged; Narcotics; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

Cocaine abuse is a common clinical problem among opioid-dependent patients who are in methadone maintenance treatment. In an open prospective study, 16 DSM-III-R, cocaine-dependent, methadone maintenance treatment patients were treated with fluoxetine, at a mean dose of 45 mg/day for 9 weeks. Eleven subjects (69%) were infected with the human immunodeficiency virus. Cocaine use was significantly reduced by the end of treatment, although most subjects did not achieve abstinence. Comparison of intake to week 9 showed a significant decrease in self-reported cocaine use, craving, and quality of high. Actual cocaine use was measured by a quantitative analysis of cocaine and benzoylecgonine (BE) concentrations in plasma and urine. Median BE and cocaine concentrations in urine decreased significantly from intake to week 9 of fluoxetine treatment. This decrease would not have been detected if BE had been measured only qualitatively, as present or absent in the urine. Fluoxetine was well tolerated in combination with methadone and did not appear to alter methadone concentrations in plasma. Few adverse effects were noted. No subjects had to discontinue fluoxetine. Fluoxetine may be a promising treatment approach for cocaine abuse in methadone maintenance patients. Quantitative determination of exact cocaine and BE concentrations in biofluids may be a more accurate method of measuring cocaine use outcome than qualitative urinalysis.

Topics: Adult; Cocaine; Female; Fluoxetine; Humans; Male; Methadone; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Substance-Related Disorders

A validity study of eight commercial urine assays for detection of cocaine metabolite was performed on clinical specimens collected from human subjects who received single 20-mg intravenous doses of cocaine hydrochloride. The specimens were collected under controlled conditions and analyzed in random order under blind conditions. Benzoylecgonine concentration in each specimen also was determined by gas chromatography/mass spectrometry (GC/MS). Mean times of detection of the last positive specimen (greater than or equal to 300 ng/mL of benzoylecgonine equivalents) after cocaine administration varied among seven of the commercial tests from 16.9 to 52.9 h in the following ascending order: Toxi-Lab less than TDx = EMIT dau = EMIT st less than Abuscreen less than Coat-A-Count = Double Antibody. In contrast, a commercial spot test (KDI Quik Test) which was evaluated for detection of cocaine metabolite produced both false positives and false negatives for benzoylecgonine and was not considered to be a valid test for detection of cocaine metabolite. Half-lives of excretion of benzoylecgonine among four subjects varied from 5.9 to 7.9 h, and overall recovery of benzoylecgonine varied from 15.0 to 34.3% of the administered dose of cocaine.

Topics: Adult; Cocaine; Gas Chromatography-Mass Spectrometry; Humans; Injections, Intravenous; Male; Radioimmunoassay; Substance-Related Disorders

A comprehensive validity assessment study was performed on eight commercial urine assays for detection of cocaine use. Sensitivity, specificity, and accuracy of each assay were evaluated by analyzing, in random order and under blind conditions, specimens spiked with known drug concentrations and clinical specimens obtained from human subjects after intravenous cocaine use. Commercial assay results were compared with gas chromatography/mass spectrometry (GC/MS) assay of the same specimens for benzoylecgonine. All of the assays examined were determined to have utility in screening for cocaine use, with the exception of the KDI Quik Test, which was not a reliable test for detection of cocaine use. Major differences in sensitivity, specificity, and confirmation rate by GC/MS were noted among the assays, differences which should be taken into consideration when implementing a urine screening test for cocaine use or interpreting test results involving use of these assays.

Topics: Adult; Cocaine; Gas Chromatography-Mass Spectrometry; Humans; Injections, Intravenous; Male; Substance-Related Disorders

This study presents a retrospective analysis of the prevalence of drug abuse in Shanghai by hair analysis. Files and toxicology analysis results of a total of 5,610 cases requesting for hair analysis of abused drugs at the Academy of Forensic Science (AFS) in Shanghai over 12 months between August 2018 and July 2019 were reviewed. All cases of drug abuse identified by hair analysis were from the public security organs in Shanghai, China. Hair samples were analyzed for drugs of abuse and related metabolites, mainly including amphetamine (AMP), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), tetrahydrocannabinol (THC), ketamine (K), norketamine (NK), cocaine (COC), benzoylecgonine, morphine, 6-acetylmorphine, flunitrazepam, and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Among the 5,610 cases, 1,713 (30.5%) were positive for drugs of abuse, with amphetamine-type stimulants (ATS) (57%), including amphetamines (AMP and MA) (48%), MDMA and MDA (9%), being the most frequently detected drugs, followed by THC (14%), COC (8%), 5-MeO-DIPT (8%), and K (7%). The majority (75%) of positive hair samples were from male subjects. Overall, 77% of abusers were younger than 44 years old. The proportion of female subjects (22.3%) under 24 years was larger than that of male subjects (7.8%). There were 132 cases (7.7%) in which more than one type of drug was detected among 1,713 drug-positive cases. The most common combination was MDMA and K. The present study characterizes the current toxicological profile of drug abuse cases and provides a scientific basis for drug abuse prevention. Moreover, the hair concentration distributions of the commonly abused drugs in positive cases have been reported.

Topics: 3,4-Methylenedioxyamphetamine; Adult; Amphetamines; Central Nervous System Stimulants; China; Chromatography, Liquid; Cocaine; Female; Hair; Hair Analysis; Humans; Illicit Drugs; Male; Methamphetamine; Morphine Derivatives; N-Methyl-3,4-methylenedioxyamphetamine; Prevalence; Retrospective Studies; Substance Abuse Detection; Substance-Related Disorders; Tandem Mass Spectrometry

Recent publications have explored the possibility of using fingerprints to confirm drug use, but none has yet dealt with environmental contamination from fingertips. Here we explored the possibility of establishing an environmental cutoff for drug testing from a single fingerprint.. Fingerprint samples (n = 100) were collected from the hands of 50 nondrug users before and after handwashing to establish separate environmental cutoff values and testing protocols for cocaine, benzoylecgonine, heroin, and 6-monoacetylmorphine. The cutoff was challenged by testing the fingerprints of drug-free volunteers after shaking hands with drug users. Fingerprints from patients who testified to taking cocaine (n = 32) and heroin (n = 24) were also collected and analyzed.. A different cutoff value needed to be applied, depending on whether the fingerprints were collected as presented or after handwashing. Applying these cutoffs gave a 0% false-positive rate from the drug-free volunteers. After application of the cutoff, the detection rate (compared to patient testimony) for washed hands of patients was 87.5% for cocaine use and 100% for heroin use.. Fingerprints show enhanced levels of cocaine, heroin, and their respective metabolites in patients who testified to taking the substances, compared with the population of naïve drug users surveyed, and a cutoff (decision level) can be established. The cutoff is robust enough to account for small increases in analyte observed after secondary transfer.

Topics: Case-Control Studies; Cocaine; Fingers; Hand Disinfection; Heroin; Humans; Limit of Detection; Morphine Derivatives; Reproducibility of Results; Skin; Substance Abuse Detection; Substance-Related Disorders

Analysis of student consumption of illicit drugs (ID) by school population surveys (SPS) provides information useful for prevention, but the results may be influenced by subjective factors. We explored wastewater (WW) analysis to improve the information.. We used WW analysis to measure ID consumption in eight secondary schools in Italy in 2010-13 (students aged 15-19). Samples were collected from the sewage pipes of the schools during lessons for one week each year. Samples were analysed by mass spectrometry to measure ID and consumption by students was compared to that of the general population.. We found THCCOOH (human metabolite of THC) concentrations in 2010 indicating significant consumption of cannabis in all the schools and benzoylecgonine (human metabolite of cocaine) suggesting a limited consumption of cocaine in all but one school. Morphine was only found in traces, and amphetamine, methamphetamine, ecstasy, ketamine and mephedrone were not detectable. Repeated analysis showed cannabis stable until 2012 with increases in 2013, low cocaine and morphine levels, and none of the other ID.. WW analysis suggested that students used amounts of cannabis comparable to the general population, with low, sporadic use of cocaine and opioids, but excluded the use of significant amounts of amphetamine, methamphetamine, ecstasy, ketamine and mephedrone. WW analysis was useful to confirm SPS figures and provides complementary findings for effective prevention strategies. This is the first time WW analysis has been used to investigate consumption of a large number of ID and new psychoactive substances (NPS) in schools.

Topics: Amphetamine; Cannabinoids; Cannabis; Cocaine; Humans; Illicit Drugs; Italy; Ketamine; Mass Spectrometry; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Substance Abuse Detection; Substance-Related Disorders; Wastewater

Individuals with mild or borderline intellectual disability (MBID) are at risk of substance use (SU). At present, it is unclear which strategy is the best for assessing SU in individuals with MBID. This study compares three strategies, namely self-report, collateral-report, and biomarker analysis.. In a sample of 112 participants with MBID from six Dutch facilities providing care to individuals with intellectual disabilities, willingness to participate, SU rates, and agreement between the three strategies were explored. The Substance use and misuse in Intellectual Disability - Questionnaire (SumID-Q; self-report) assesses lifetime use, use in the previous month, and recent use of tobacco, alcohol, cannabis, and stimulants. The Substance use and misuse in Intellectual Disability - Collateral-report questionnaire (SumID-CR; collateral-report) assesses staff members' report of participants' SU over the same reference periods as the SumID-Q. Biomarkers for SU, such as cotinine (metabolite of nicotine), ethanol, tetrahydrocannabinol (THC), and its metabolite THCCOOH, benzoylecgonine (metabolite of cocaine), and amphetamines were assessed in urine, hair, and sweat patches.. Willingness to provide biomarker samples was significantly lower compared to willingness to complete the SumID-Q (p<0.001). Most participants reported smoking, drinking alcohol, and using cannabis at least once in their lives, and about a fifth had ever used stimulants. Collateralreported lifetime use was significantly lower. However, self-reported past month and recent SU rates did not differ significantly from the rates from collateral-reports or biomarkers, with the exception of lower alcohol use rates found in biomarker analysis. The agreement between self-report and biomarker analysis was substantial (kappas 0.60-0.89), except for alcohol use (kappa 0.06). Disagreement between SumID-Q and biomarkers concerned mainly over-reporting of the SumID-Q. The agreement between SumID-CR and biomarker analysis was moderate to substantial (kappas 0.48 - 0.88), again with the exception of alcohol (kappa 0.02).. In this study, the three strategies that were used to assess SU in individuals with MBID differed significantly in participation rates, but not in SU rates. Several explanations for the better-than-expected performance of self- and collateral-reports are presented. We conclude that for individuals with MBID, self-report combined with collateralreport can be used to assess current SU, and this combination may contribute to collaborative, early intervention efforts to reduce SU and its related harms in this vulnerable group.

Topics: Adult; Alcohol Drinking; Amphetamine-Related Disorders; Amphetamines; Biomarkers; Cocaine; Cocaine-Related Disorders; Cotinine; Dronabinol; Ethanol; Female; Hair; Humans; Intellectual Disability; Male; Marijuana Smoking; Middle Aged; Netherlands; Self Report; Severity of Illness Index; Smoking; Substance Abuse Detection; Substance-Related Disorders; Sweat; Urine; Young Adult

Opioids and cocaine are widely used at present, both for recreational purposes and as drugs of abuse. This raises the need to develop new analytical methods specifically designed for the simultaneous detection of several drugs of abuse in biological samples. In this work, dispersive liquid-liquid microextraction (DLLME) was assessed as a new sample treatment for the simultaneous extraction of morphine (MOR), 6-acetylmorphine (6AM), cocaine (COC), benzoylecgonine (BZE) and methadone (MET) from human plasma. Preliminary assays were done before developing an experimental design based on a Uniform Network Doehlert which allowed the optimum extraction conditions to be identified, namely: a volume of extractant solvent (chloroform) and dispersant solvent (acetonitrile) of 220 µl and 3.2 ml, respectively; 0.2 g of NaCl as a salting-out additive; pH 10.6 and ultrasound stirring for 3.5 min. The resulting extracts were analyzed by high-performance liquid chromatography with photodiode array detection (HPLC-PDA), using an XBridge® RP18 column (250 × 4.6 mm i.d., 5 µm particle size). Calibration graphs were linear over the concentration range 0.1-10 µg ml⁻¹, and detection limits ranged from 13.9 to 28.5 ng ml⁻¹. Precision calculated at three different concentration levels in plasma was included in the range 0.1-6.8% RSD. Recoveries of the five drugs were all higher than 84% on average. Finally the proposed method was successfully applied to 22 plasma samples from heroin, cocaine and/or methadone users, and the most frequently detected drug was benzoylecgonine, followed by methadone, cocaine and morphine.

Topics: Analytic Sample Preparation Methods; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Cocaine; Humans; Hydrogen-Ion Concentration; Illicit Drugs; Limit of Detection; Liquid Phase Microextraction; Methadone; Morphine; Morphine Derivatives; Opiate Substitution Treatment; Photometry; Reproducibility of Results; Solubility; Spectrophotometry, Ultraviolet; Substance Abuse Detection; Substance-Related Disorders; Ultrasonics

Illicit drug consumption in five cities in South Korea was estimated by analyzing 17 drug residues in untreated wastewater samples collected during the Christmas and New Year period of 2012-13. Only methamphetamine, amphetamine, and codeine were detected at concentrations of tens of nanograms per liter or even lower concentrations in more than 90% of the samples. Other illicit drug residues (including cocaine, methadone, and benzoylecgonine) that have been detected frequently in wastewater from other countries were not found in this study. Methamphetamine was found to be the most widely used illicit drug in South Korea, and the estimated average consumption rate was 22 mg d(-1) (1000 people)(-1). This rate is, for example, 2-5 times lower than the estimated average consumption rates in Hong Kong and other parts of China and 4-80 times lower than the estimated average consumption rates in cities in Western countries. It should be noted that the wastewater samples analyzed in this study were collected during a holiday season, when daily consumption of illicit drugs is often higher than on an average day. The methamphetamine usage rates were calculated for different cities in South Korea, and the usage rates in smaller cities was higher (2-4 times) than the average.

Topics: Amphetamine; Amphetamines; Cities; Cocaine; Humans; Illicit Drugs; Methamphetamine; Republic of Korea; Substance Abuse Detection; Substance-Related Disorders; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical

A method based on sample preparation by solid phase extraction and analysis by liquid chromatography and mass spectrometry was validated and used for simultaneous analysis of cocaine, benzoylecgonine and cotinine in samples collected at the major wastewater treatment plant in the city of Lisbon. The aim was to estimate the consumption of both cocaine and nicotine in this community and establish an index involving both drugs supported by the relevance of nicotine as a significant anthropogenic marker. The study was made on two different weekdays during a month in order to evaluate patterns of consumption outside weekends. Cocaine and nicotine ingestion levels were back-calculated and expressed as mass of pure drugs consumed per day and per 1000 inhabitants (mean: 0.604 g and 5.860 g respectively). Cocaine was also expressed on the basis of local drug purity levels (33.7%) with a corresponding increase on dose assessments, and community drug abuse profiles. The authors sustain that this approach should always be included in drug studies of this kind allowing a better drug abuse assessment. No significant different patterns of consumption were obtained during the working days studied with the exception of one case coincident with a national holiday that showed an increased typical profile found on other non-working day studies, namely weekends. A fairly significant relationship was found between nicotine and cocaine consumption that should be further evaluated in future studies. Pharmacokinetic considerations were made and proposed for cocaine assessment based on the impact on back calculations after common simultaneous consumption of cocaine and ethanol.

Topics: Chromatography, Liquid; Cocaine; Environmental Monitoring; Humans; Illicit Drugs; Nicotine; Solid Phase Extraction; Substance-Related Disorders; Tandem Mass Spectrometry; Wastewater; Water Pollutants, Chemical; Water Pollution, Chemical

This communication reports the blood concentrations of alcohol and drugs from 376 cases of alleged driving under the influence of drugs analysed at the Forensic Science Service Chorley and London laboratories between February 2010 and March 2011. The samples were analysed for alcohol, amphetamine, benzodiazepines, cocaine, MDMA, opiates, γ-hydroxybutyrate (GHB), ketamine, methadone and methylmethcathinone (the 4-isomer of which is known as mephedrone). The results were interpreted with respect to the number and type of drugs of abuse detected and the concentrations measured. Alcohol was quantified in 113 cases (30%), and of these a level in excess of the prescribed UK limit for driving of 80 mg% was present in 90 cases. In 80 cases, only the concentration of alcohol was measured, the concentrations of both drugs and alcohol were measured in 33 cases. In the remaining 263 cases, only the concentrations of relevant drugs of abuse were measured. The most common drug of abuse quantified was cocaine which was detected in 92 cases, either as the active drug or as its major metabolite benzoylecgonine, followed by diazepam which was quantified in 76 cases. Concentrations of some new drugs, and drugs rarely reported in driving under the influence cases are also presented.

Topics: Adolescent; Adult; Amphetamine; Automobile Driving; Central Nervous System Depressants; Chromatography, Liquid; Cocaine; Diazepam; England; Ethanol; Female; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Ketamine; Male; Methadone; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Nordazepam; Sodium Oxybate; Substance Abuse Detection; Substance-Related Disorders; Wales; Young Adult

The measurement of illicit drug metabolites in raw wastewater is increasingly being adopted as an approach to objectively monitor population-level drug use, and is an effective complement to traditional epidemiological methods. As such, it has been widely applied in western countries. In this study, we utilised this approach to assess drug use patterns over nine days during April 2011 in Hong Kong. Raw wastewater samples were collected from the largest wastewater treatment plant serving a community of approximately 3.5 million people and analysed for excreted drug residues including cocaine, ketamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and key metabolites using liquid chromatography coupled with tandem mass spectrometry. The overall drug use pattern determined by wastewater analysis was consistent with that have seen amongst people coming into contact with services in relation to substance use; among our target drugs, ketamine (estimated consumption: 1400-1600 mg/day/1000 people) was the predominant drug followed by methamphetamine (180-200 mg/day/1000 people), cocaine (160-180 mg/day/1000 people) and MDMA (not detected). The levels of these drugs were relatively steady throughout the monitoring period. Analysing samples at higher temporal resolution provided data on diurnal variations of drug residue loads. Elevated ratios of cocaine to benzoylecgonine were identified unexpectedly in three samples during the evening and night, providing evidence for potential dumping events of cocaine. This study provides the first application of wastewater analysis to quantitatively evaluate daily drug use in an Asian metropolitan community. Our data reinforces the benefit of wastewater monitoring to health and law enforcement authorities for strategic planning and evaluation of drug intervention strategies.

Topics: Chromatography, Liquid; Cocaine; Hong Kong; Humans; Ketamine; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Pilot Projects; Substance Abuse Detection; Substance-Related Disorders; Tandem Mass Spectrometry; Time Factors; Urban Population; Wastewater

The aim of this study was to integrally address the uncertainty associated with all the steps used to estimate community drug consumption through the chemical analysis of sewage biomarkers of illicit drugs. Uncertainty has been evaluated for sampling, chemical analysis, stability of drug biomarkers in sewage, back-calculation of drug use (specific case of cocaine), and estimation of population size in a catchment using data collected from a recent Europe-wide investigation and from the available literature. The quality of sampling protocols and analytical measurements has been evaluated by analyzing standardized questionnaires collected from 19 sewage treatments plants (STPs) and the results of an interlaboratory study (ILS), respectively. Extensive reviews of the available literature have been used to evaluate stability of drug biomarkers in sewage and the uncertainty related to back-calculation of cocaine use. Different methods for estimating population size in a catchment have been compared and the variability among the collected data was very high (7-55%). A reasonable strategy to reduce uncertainty was therefore to choose the most reliable estimation case by case. In the other cases, the highest uncertainties are related to the analysis of sewage drug biomarkers (uncertainty as relative standard deviation; RSD: 6-26% from ILS) and to the back-calculation of cocaine use (uncertainty; RSD: 26%). Uncertainty can be kept below 10% in the remaining steps, if specific requirements outlined in this work are considered. For each step, a best practice protocol has been suggested and discussed to reduce and keep to a minimum the uncertainty of the entire procedure and to improve the reliability of the estimates of drug use.

Topics: Biomarkers; Cocaine; Humans; Population Density; Sewage; Solid Phase Extraction; Substance-Related Disorders; Surveys and Questionnaires; Uncertainty; Water Pollutants, Chemical

The use of oral fluid (OF) as an alternative matrix for the detection of drugs of abuse has increased over the last decade, leading to the need for a rapid, simple, and reliable on-site OF testing device. Four on-site OF drug testing devices (Dräger DrugTest 5000, Cozart DDS, Mavand Rapid STAT, and Innovacon OrAlert) were evaluated on 408 volunteers at drug treatment centers. UPLC-MS-MS results were used as reference to determine sensitivity, specificity and accuracy for each device, applying Belgian legal confirmation cutoffs for benzoylecgonine, cocaine, and THC (10 ng/mL); morphine and 6-acetylmorphine (5 ng/mL); and amphetamine and 3,4-methylenedioxymethylamphetamine (25 ng/mL). Sensitivity for cocaine was 50%, 50%, 27%, and 11% for DrugTest, OrAlert, Rapid STAT, and DDS 806, respectively. For opiates, sensitivities were 84%, 73%, 77%, and 65%, respectively. For THC, the sensitivities were 81%, 23%, 43%, and 28%, respectively. For amphetamines, the sensitivities were 75%, 33%, 17%, and 67%, respectively. Specificity was >88% for opiates and THC, > 90% for amphetamines, and > 97% for cocaine. All tests showed good specificity. DrugTest had the highest sensitivity, although it was still low for some analytes.

Topics: Amphetamine; Chromatography, Liquid; Cocaine; Dronabinol; Humans; Methamphetamine; Morphine Derivatives; Reproducibility of Results; Saliva; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Tandem Mass Spectrometry

This manuscript reports, for the first time, a monitoring study analysing wastewater and associated suspended particulate matter (SPM) to determine the concentration of drugs of abuse and metabolites in wastewater influent. The monitoring of SPM is crucial for target analytes because, depending on their physico-chemical properties, they may partition to particulates; thus, analysis of wastewater only will result in under-reporting of the concentration of target analytes in the sample. A daily one week monitoring study was carried out at a WWTP serving one of the largest cities in the Czech Republic; representing the first comprehensive application of the sewage epidemiology approach in the Czech Republic. In total, 60 analytes were targeted in the monitoring programme including stimulants, opioid and morphine derivatives, benzodiazepines, antidepressants, dissociative anaesthetics, drug precursors and their metabolites. Analysis of SPM determined that significant proportions of some compounds were present on the solids. For example, 21.0-49.8% of the total concentration of EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) in the sample was determined on SPM and 11.2-19.6% of methadone. The highest proportion on SPM was determined for fluoxetine in the range 68.1-79.6%, norfluoxetine 46.6-61.9% and amitriptyline 21.8-51.2%. In contrast, some compounds presented very little partitioning to SPM. Less than 5% was determined partitioned to SPM over the week period for analytes including cocaine, benzoylecgonine, cocaethylene, amphetamine, methamphetamine, MDMA (3,4-methylenedioxymethamphetamine), codeine, dihydrocodeine, tramadol, nortramadol, oxazepam and ephedrine. Determined concentrations in wastewater influent were subsequently utilised in the sewage epidemiology approach to estimate drug consumption, in the community from which the wastewater was derived. This back-calculation was updated for the first time to include the concentration of analytes present on SPM. The consumption of methamphetamine and MDMA was determined to be especially high in the studied community in relation to other European countries, while cocaine and methadone consumption was relatively low. This manuscript shows that in order to apply the sewage epidemiology approach, SPM analysis is required for some compounds; whereas for others the partitioning is small and one may regard this as negligible.

Topics: Cocaine; Czech Republic; Environmental Monitoring; Illicit Drugs; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Pyrrolidines; Sewage; Substance-Related Disorders; Wastewater; Water Pollutants, Chemical; Water Pollution, Chemical

Accurate information on drug use in communities is essential if health, social and economic harms associated with illicit drug use are to be addressed efficiently. In most countries population drug use is estimated indirectly via surveys, medical presentations and police and custom seizures. All of these methods have at least some problems due to bias, small samples and/or long time delays between collecting the information and analysing the results. Recently the direct quantification of drug residues in wastewater has shown promise as a means of monitoring drug use in defined geographical areas. In this study we measured 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine and benzoylecgonine in sewage inflows in metropolitan and regional areas of Australia and compared these data with published European data. Cocaine use was small compared to European cities (p<0.001) but was compensated for by much greater consumption of methamphetamine (p<0.001) and MDMA (p<0.05). MDMA was more popular in regional areas (p<0.05) whereas methamphetamine and cocaine were mainly consumed in the city (p<0.05). Greater than 5-fold increases in MDMA use were detected on weekends (p<0.001). This approach has the potential to improve our understanding of drug use in populations and should be further developed to improve prevention and treatment programs.

Topics: Australia; Cocaine; Humans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Sewage; Substance-Related Disorders; Suburban Population; Time Factors; Urban Population

Postmortem tissues (e.g. liver, kidney) have been long used in forensic applications especially in those cases where blood is unavailable. The aim of this paper is to demonstrate the importance of the information provided to the forensic toxicologist at the time of carrying out the toxicological analysis, especially in cases where the samples commonly used in forensic toxicology are unavailable. This work describes the toxicological findings in a violent death resulting from a man who was hit by a train. Vitreous humor, liver and kidney were sent for toxicological analysis, once it was not possible to obtain blood and urine. The validated procedures used in the routine casework of Forensic Toxicology Laboratory of the Centre Branch of the National Institute of Legal Medicine, were applied in the analysis of liver, kidney and vitreous humor, using gas chromatography-mass spectrometry after solid-phase extraction and gas chromatography-flame ionization detector for the analysis of drugs of abuse and ethanol, respectively. Morphine, codeine, cocaine, benzoylecgonine and ecgonine methyl ester were found in the liver and in the kidney and no ethanol was found in the vitreous humor. The method validation included the study of specificity, selectivity, limits of detection, recovery and carryover. Although blood and urine are the most common and preferred matrices used for toxicological studies involving drugs of abuse, sometimes the choice of specimen is determined by the case under investigation. The forensic pathologist must be aware that relevant information must be provided so that the toxicological analysis can be conducted in accordance with case history, particularly when the only samples available for analysis are these "unconventional" specimens, since the interpretation of the obtained results is more difficult.

Topics: Adult; Cocaine; Codeine; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Illicit Drugs; Kidney; Liver; Male; Morphine; Narcotics; Substance-Related Disorders; Vitreous Body

Recent reports in Europe suggest a decline in 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) use, but quantifiable and objective measurement is unavailable. The global extent of changes in MDMA and related stimulant use is also unclear. This study aims to quantify changes in MDMA use in Australia and determine whether these changes have been accompanied by differing amounts of other stimulant use.. We acquired information on recent use of MDMA and related illicit stimulants in Australia using the method of wastewater analysis. Untreated wastewater samples collected from three metropolitan treatment plants in Adelaide from May to July 2009 and the same months in 2010 were analyzed. Concentrations of MDMA, methamphetamine, and benzoylecgonine (a metabolite of cocaine) were determined using solid phase extraction-liquid chromatography- tandem mass spectrometry. Weekly consumed doses of MDMA, methamphetamine, and cocaine per 1,000 people were estimated.. From 2009 to 2010, weekly consumption of MDMA decreased from mean of 4.52 (SEM = 0.74) doses/week per 1,000 people to 0.08 (0.01) doses/week per 1,000 people (p < .001); weekly consumption of methamphetamine increased from a mean of 48.35 (6.13) doses/week per 1,000 people to 68.13 (5.33) doses/week per 1,000 people (p < .05); and weekly consumed doses of cocaine did not significantly change. Local roadside saliva testing data also showed that the MDMA-positive test rate decreased from 0.30% to 0.05% and the methamphetamine-positive test rate increased from 1.43% to 1.52% during the past 2 years.. This study shows a 50-fold decrease in consumed doses of MDMA with a rise in methamphetamine use in Australia over a 1-year period.

Topics: Australia; Chromatography, High Pressure Liquid; Cocaine; Cross-Sectional Studies; Humans; Illicit Drugs; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Population Surveillance; Saliva; Solid Phase Extraction; Substance Abuse Detection; Substance-Related Disorders; Tandem Mass Spectrometry; Urban Health; Waste Disposal, Fluid; Water Supply

Driving under the influence of drugs is a major problem worldwide. At the moment, several countries have adopted a 'per se' legislation to address this problem. One of the key elements in the enforcement process is the possibility of rapid on-site screening tests to take immediate administrative measures. In this study, the reliability of three oral fluid screening devices (Mavand RapidSTAT, Securetec Drugwipe-5(+), and Dräger DrugTest 5000) was assessed by comparing their on-site results with confirmatory GC-MS plasma analysis. Our results demonstrate that for amphetamine screening, the oral fluid on-site devices on the market today are certainly sensitive enough. RapidSTAT, Drugwipe-5(+), and DrugTest 5000 demonstrated respectively a sensitivity of 93%, 100% and 92% for amphetamine/MDMA. For cocaine screening, sensitivities of 75%, 78% and 67% were obtained for the RapidSTAT, Drugwipe-5(+), and DrugTest 5000 devices, respectively. The studied devices were able to detect about 70% of all cannabis users in a roadside setting. However, a newer version of the DrugTest 5000 test cassette demonstrated a sensitivity of 93%, indicating an increased detection of Delta(9)-tetrahydrocannabinol using 'new generation' oral fluid screening tests with lowered cut-offs. Due to these promising results police officers and judicial experts are keen to use oral fluid screening devices. They believe that their ease of use and diminished amount of false positive results in comparison with urine screening will lead to more roadside tests and more appropriate juridical measures.

Topics: Amphetamines; Automobile Driving; Cocaine; Dronabinol; Forensic Toxicology; Humans; Morphine; Narcotics; Saliva; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders

In this study of wastewater treatment plants in three Canadian cities, selected illicit drugs, including cocaine and its major metabolite, benzoylecgonine (BE), amphetamine, methamphetamine and ecstasy (i.e. MDMA) were detected in untreated wastewater. Cocaine was the most widely used illicit drug at a median level for the 3 cities of 15.7 doses per day per 1000 people. For the other drugs, the median doses per day per 1000 people were 1.8 for amphetamine, 4.5 for methamphetamine and 0.4 for ecstasy. Methamphetamine use was highest in the largest city and cocaine use was lowest in the smallest city. Removal of the illicit drugs by wastewater treatment was generally >50%, except in a WWTP that uses primary treatment. The community consumption estimate for ecstasy in the present study is far below published estimates of the prevalence of ecstasy use among the Canadian population, which may be due to only occasional use of ecstasy.

Topics: Amphetamine; Canada; Cities; Cocaine; Illicit Drugs; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Solid Phase Extraction; Substance Abuse Detection; Substance-Related Disorders; Waste Disposal, Fluid; Water Pollutants, Chemical; Water Pollution, Chemical

There is a paucity of literature detailing the disposition of drugs in bone and bone marrow. Infrequently, in deaths involving skeletonized remains, fragmentation, decomposition, and exsanguination, traditional specimens may be unavailable for toxicological testing. This study examined the utility of bone for the detection of benzodiazepines, opiates, cocaine and metabolites, and basic drugs in 39 cases. Cases were identified on the basis of a positive blood result. After specimen preparation, samples were assayed by liquid-liquid or solid phase extraction with gas chromatographic and gas chromatographic mass spectrometric detection. The majority of decedents were white males with 28% of individuals between the ages of 41 to 50 years. The cause of death was drug intoxication in 22 cases. The most prevalent drugs detected in the blood males and females were opiates and bases. Morphine, codeine, and oxycodone were detected in bone, whereas 6-acetylmorphine and hydrocodone were absent. For alkaline extractable drugs, in only 57% of blood positive specimens, the corresponding bone was also positive. These included antidepressants and antihistamines. Diazepam and nordiazepam were detected in the bone of all blood positive cases. Bone concentrations were higher than blood levels. Benzoylecgonine was the most common cocaine analyte detected in bone. These data demonstrated that drugs may be detected in bone using current technologies and that in general concentrations were higher than those observed in corresponding blood specimens. A negative result in bone, however, should be interpreted with caution because multiple factors determine the deposition of a drug in this matrix.

Topics: Adult; Aged; Aged, 80 and over; Benzodiazepines; Bone and Bones; Cocaine; Female; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Infant; Infant, Newborn; Male; Middle Aged; Narcotics; Pharmaceutical Preparations; Substance-Related Disorders

We used hair testing to investigate the prevalence of unsuspected exposure to cocaine in a group of preschool children presenting to an urban pediatric emergency department without signs or symptoms suggestive of exposure. Hair samples were obtained from 90 children between 18 months and 5 years of age attending the emergency room of Hospital del Mar in Barcelona, Spain. In 85 cases, hair samples from the accompanying parent were also provided. The samples were analyzed for the presence of cocaine and benzoylecgonine by gas chromatography-mass spectrometry, which also determined opiates and amphetamines. Parental sociodemographics, possible drug history, and information on the child's features were recorded. Hair samples from 21 children (23.3%) were positive for cocaine (concentration range 0.3-5.96 ng/mg of hair) with 1 sample also positive for 3,4-methylenedioxymethamphetamine and another for opiates. In 88% of the positive cases, cocaine was also found in the hair of the accompanying parent (15 of 17 matched parent-child hair samples). Parental sociodemographics were associated neither with children's exposure to cocaine nor with somatometry of children at birth. However, the behavioral patterns with potential harmful effects for the child's health (eg, tobacco smoking, cannabis, benzodiazepines and/or antidepressants use, and shorter breast-feeding time) were significantly higher in the parents of exposed children. A statistically higher percentage of exposed children were in the lower weight percentile group compared with the nonexposed children. In the light of these results, we advocate general hair screening to disclose exposure to cocaine and other drugs of abuse in children from risky environments, which could provide the basis for specific social and health interventions.

Topics: Amphetamines; Cannabis; Child; Cocaine; Female; Gas Chromatography-Mass Spectrometry; Hair; Humans; Infant, Newborn; Marijuana Abuse; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Smoking; Social Class; Spain; Substance Abuse Detection; Substance-Related Disorders

The diffusion and trends in use of each substance is a basic information in policy planning of strategies aiming at deterrence of drug abuse or in the organization of the fight against drug trafficking. The actual diffusion of illicit drugs in a population is hardly measurable, but, among the various measures available, the analysis of waste water plants represents one of the most reliable source of data. We analyzed waste water in order to monitor illicit drug use by local population. We investigated the use of cocaine and heroin in the city of Florence, Italy, over a 1-year (July 2006-June 2007) period using state-of-the-art measuring techniques from waste water samples. Cocaine, benzoylecgonine, and morphine were determined in water samples by gas chromatography-mass spectrometer, and the amount of illicit substance was estimated. Data indicate for cocaine a bimodal distribution (December and March), while heroin showed a main peak in April. The heroin-to-cocaine use ratio in terms of estimated doses per month ranged from 0.11 to 0.76, representing new evidence of wider distribution of cocaine than heroin in Florence. Waste water analysis can become a valuable tool in monitoring use of illicit drugs over time. In particular, it can highlight changes in the magnitude and relative use of illicit drug at a population level thereby becoming useful to develop strategies against drug trafficking and abuse. If routinely performed, it can be part of Epidemiologic Surveillance Programmes on drug abuse.

Topics: Cocaine; Gas Chromatography-Mass Spectrometry; Heroin; Humans; Illicit Drugs; Italy; Morphine; Narcotics; Seasons; Substance-Related Disorders; Waste Disposal, Fluid; Water

To determine the utility of community-wide drug testing with wastewater samples as a population measure of community drug use and to test the hypothesis that the association with urbanicity would vary for three different stimulant drugs of abuse.. Single-day samples were obtained from a convenience sample of 96 municipalities representing 65% of the population of the State of Oregon.. Chemical analysis of 24-hour composite influent samples for benzoylecgonine (BZE, a cocaine metabolite), methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The distribution of community index drug loads accounting for total wastewater flow (i.e. dilution) and population are reported.. The distribution of wastewater-derived drug index loads was found to correspond with expected epidemiological drug patterns. Index loads of BZE were significantly higher in urban areas and below detection in many rural areas. Conversely, methamphetamine was present in all municipalities, with no significant differences in index loads by urbanicity. MDMA was at quantifiable levels in fewer than half the communities, with a significant trend towards higher index loads in more urban areas. CONCLUSION; This demonstration provides the first evidence of the utility of wastewater-derived community drug loads for spatial analyses. Such data have the potential to improve dramatically the measurement of the true level and distribution of a range of drugs. Drug index load data provide information for all people in a community and are potentially applicable to a much larger proportion of the total population than existing measures.

Topics: Cocaine; Environmental Monitoring; Epidemiological Monitoring; Humans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Oregon; Rural Population; Substance Abuse Detection; Substance-Related Disorders; Urban Population; Waste Disposal, Fluid; Water Pollutants, Chemical

The differentiation between systemic exposure and external contamination for certain drug groups has been frequently referred to as one of the limitations of in drug testing in hair. When hair samples are used, three steps are usually employed in order to minimise the possibility of external contamination causing a misinterpretation. The first consists of decontaminating hair samples by washing the hair before analysis, the second is the detection of the relevant metabolites in the hair samples and the third is the use of cut-off levels. Difficulty in the interpretation arises when metabolites are not detected either due to external contamination of the hair or low doses of the drugs used. A wash protocol needs to be practical and ideally remove any drug deposited on the external portion of the hair. We propose an additional step that helps considerably in the interpretation of the results with the aim to establish a consensus: the analysis of the wash residue (W) and its comparison with the levels detected in hair (H). The wash residue is the remainder of a quick wash with methanol which is dried and reconstituted in buffer before analysis. The detection of small quantities of analytes that are not susceptible to external contamination in the wash residue, such as metabolites or drugs such as dihydrocodeine, indicates that the washing procedure is in fact able to remove drugs from the hair shaft. Where the W/H ratio is less then 0.1 or null, it would tend to indicate drug use as opposed to environmental contamination. Where the W/H ratio is above 0.1 but less than 0.5, it is likely to indicate possible use possibly combined with a level of external contamination. A W/H ratio greater than 0.5 is likely to indicate that the source of most of the drug in the wash residue is from external contamination. In this last case, the source of levels detected in the hair is questionable, as it is not possible to be absolutely sure that all external contamination was removed, and so use cannot be confirmed. Two hundred and sixteen hair samples from a population where external contamination could be expected (Police Investigations on drug related cases) and their wash residue were analysed. The W/H ratios of 891 results were evaluated over 13 analytes. Between 74 and 100% of the analytes studied produced W/H ratios less than 0.5, in particular in cannabis (93%) and cocaine (95%), where external contamination is more likely because of the way the drug is used. The data

Topics: Amphetamines; Cannabinoids; Cocaine; Dopamine Uptake Inhibitors; Drug Contamination; Drug Residues; Environmental Exposure; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Hair; Humans; Methanol; Narcotics; Solvents; Substance Abuse Detection; Substance-Related Disorders

A solid phase extraction (SPE) method has been developed and applied in conjunction with a previously reported liquid chromatography tandem mass spectrometry (LC-MS-MS) procedure for the determination of illicit drugs and abused pharmaceuticals in treated wastewater and surface water samples at the ng L(-1) level. A full method validation was also performed and determined levels of analytical sensitivity were found to lie in the 1-10 ng L(-1) range using river water as a test sample matrix and a sample size of 500 mL. The developed procedure was successfully applied for the determination of the chosen analytes in wastewater treatment plants in Dublin, Ireland and rapidly expanding commuter towns in the surrounding counties. Cocaine was detected in 70% of the collected samples in the range of 25-489 ng L(-1), its primary metabolite, benzoylecognine (BZE) was also detected in the range of 22-290 ng L(-1). Other substances detected included morphine, Tempazepam and the primary metabolite of methadone.

Topics: Chromatography, Liquid; Cities; Cocaine; Environmental Monitoring; Humans; Illicit Drugs; Ireland; Morphine; Pharmaceutical Preparations; Pyrrolidines; Residence Characteristics; Rivers; Solid Phase Extraction; Substance-Related Disorders; Tandem Mass Spectrometry; Temazepam; Waste Disposal, Fluid; Water Pollutants, Chemical

Since concentration of drugs of abuse found in the brain better reflect drug concentration at their site of action, brain specimens are useful in the determination of the role of drugs of abuse in the cause of death. In order to allow for the routine use of brain specimens in this field, a comprehensive database with reliable reference values is needed and should include both post-mortem data for cases where drugs have been taken in therapeutic doses as well as for cases of overdose. In this study, a semi-automated extraction procedure, in combination with gas chromatography/mass spectrometry (GC-MS) using stable isotope internal standards was applied to yield reproducible, quantitative results which could be used to investigate the distribution patterns of drugs of abuse within specific regions of the brain, by analyzing several segments of both medulla oblongata and cerebellum. A homogenous distribution of unconjugated morphine, dihydrocodeine, and benzoylecgonine within the investigated segments of medulla oblongata or cerebellum could be found. However, when these two brain regions from the same case were compared to each other, significantly higher concentrations of unconjugated morphine, dihydrocodeine, and benzoylecgonine were found in the cerebellum than in the medulla oblongata.

Topics: Adolescent; Adult; Aged; Cerebellum; Cocaine; Codeine; Dopamine Uptake Inhibitors; Female; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Male; Medulla Oblongata; Middle Aged; Morphine; Narcotics; Substance Abuse Detection; Substance-Related Disorders; Tissue Distribution

Fatalities associated with fentanyl hydrochloride are increasingly seen in Massachusetts. Between September 2005 and November 2006, 5009 medicolegal investigations associated 107 deaths with licit or illicit fentanyl use, along with a co-detection of an opiate/opioid or cocaine/benzoylecognine, or both. Deaths associated with illicit fentanyl use occur in younger people (39.4 vs. 61.5 years) with higher fentanyl (17.1 ng/mL vs. 4.4 ng/mL) and lower morphine (76.9 ng/mL vs. 284.2 ng/mL) postmortem blood concentrations, and more frequent cocaine co-intoxication (65% vs. 3%), than deaths associated with illicit fentanyl use. A wide range of postmortem blood concentrations of fentanyl was detected (trace-280 ng/mL), with a minimum concentration of 7 ng/mL of fentanyl strongly associated with illicit use of fentanyl in poly-drug cases. The most commonly detected opiates/opioids in illicit fentanyl users were: morphine (29%), oxycodone (14.5%), and methadone (14.5%). Ethanol, cannabinoids, diazepam, citalopram, and diphenhydramine were each detected in greater than 10% of the licit fentanyl cases. Most fentanyl abusers died at their own home and their deaths were most often classified as accidental. Mapping of primary residences of decedents revealed conspicuous clustering of the illicit fentanyl use cases, as opposed to the random pattern in licit use cases. Fentanyl misuse is a public health problem in Massachusetts.

Topics: Accidents; Adult; Aged; Aged, 80 and over; Cannabinoids; Cause of Death; Central Nervous System Depressants; Cocaine; Dopamine Uptake Inhibitors; Drug Overdose; Ethanol; Female; Fentanyl; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Narcotics; Selective Serotonin Reuptake Inhibitors; Substance-Related Disorders

A column-switching high-performance liquid chromatographic method with UV detection for the determination of cocaine (COC) and benzoylecgonine (BZE) in human blood plasma samples is described. The method uses an alkyl-diol-silica ADS-C18 extraction precolumn. A 50- micro L plasma sample was introduced to the ADS precolumn in order to separate the analytes from proteins and endogenous compounds. The fraction containing COC and BZE was back-flushed and transferred to an Alltech mixed-mode C(18)/cation-exchange analytical column for final separation. The validation of the method revealed quantitative recoveries from 95.0 to 99.0% for COC at three different concentrations (0.5, 1.0 and 2.0 micro g mL(-1)), and from 96.0 to 99.0% for BZE at the same concentration levels with coefficients of variation <4.00% (n=5). The detection limit (signal to noise ratio (S/N)>3) was 0.03 micro g mL(-1) for all the compounds with an injection volume of 50 micro L. However, it was possible to enhance the sensitivity further by injecting larger plasma volumes, up to 200 micro L, at the same optimal conditions. The overlap of sample preparation, analysis and reconditioning of the extraction column, increase the overall sample throughput to 5 samples h(-1). The developed method has been applied to human blood plasma samples from subjects suspected of cocaine abuse.

Topics: Chromatography, High Pressure Liquid; Cocaine; Equipment Design; Humans; Hydrogen-Ion Concentration; Reference Standards; Silicon Dioxide; Solvents; Substance-Related Disorders

The present paper describes a qualitative and quantitative method for the simultaneous detection of opiates, cocaine and benzoylecgonine from human hair samples. Every step of the analytical procedure was studied to find the optimized conditions. Nine different incubation systems were examined. The influence of different pH values of samples on the isolation of analytes from the incubation media by Bond Elut cartridges and the stability of the compounds of interest in the different incubation media and conditions were investigated. The extracting power of different incubation media was studied as well. The phosphate buffer 0.1 N at pH 5 was chosen as the extraction medium in an optimized procedure for simultaneous determination of opiates, cocaine and benzoylecgonine in hair samples. The method developed was validated. Recoveries were 90% for morphine (M), 81% for 6-monoacetylmorphine (6-AM), 90% for codeine (CD), 86% for cocaine (C) and 90% for benzoylecgonine (BE). Relative standard deviation for inter-day precision was better than 12%. The limits of detection resulted as 0.05 ng/mg for M and C, as 0.08 for 6-AM and as 0.2 ng/mg for BE. Forty hair samples collected from drug abusers admitted to centers for detoxification treatment were analyzed obtaining 23 positive results for opiates and/or cocaine. Twelve hair specimens longer than 10 cm were analyzed following a sectional approach. In the six positive cases, it was interesting to find that the 6-AM/M ratio generally decreased for each sample from the proximal segment to the distal segments. Moreover, the 6-AM/M ratio was generally lower than 1 in the intermediate and distal segments.

Topics: Adolescent; Adult; Buffers; Case-Control Studies; Cocaine; Codeine; Dopamine Uptake Inhibitors; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Hair; Humans; Male; Middle Aged; Morphine; Morphine Derivatives; Narcotics; Phosphates; Substance-Related Disorders

Sixty nine participants in the United Kingdom national external quality assessment scheme for drugs of abuse in urine reported details of their sample extraction technique by questionnaire. Laboratories were categorised by differences in technique and their analytical test results compared for samples containing D-amfetamine 0.4 (4) and 0.8 (3) mg/l, morphine 0.4 (4) and 0.8 (4)mg/l, and benzoylecgonine 0.15/0.2 (2) and 0.45/0.5 (4) mg/l. Values in parentheses are numbers of samples. For amfetamine, there was no significant difference in the frequency of true positive results between liquid-liquid or solid phase extraction and the Toxi-Lab A system at 0.8 mg/l. Toxi-Lab A gave significantly fewer positives when operating below its specified threshold at 0.4 mg/l. Paradoxically, laboratories using >5 ml urine volume performed less well. Acidification of the extract before volume reduction gave significantly more true positives. For extraction of morphine, solid phase systems significantly outperformed both liquid-liquid and the Toxi-Lab A system at both 0.8 and 0.4 mg/l. No significant differences between extraction techniques were demonstrated for analysis of benzoylecgonine.

Topics: Amphetamines; Chi-Square Distribution; Cocaine; Humans; Laboratories; Morphine; Narcotics; Quality Assurance, Health Care; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Surveys and Questionnaires; United Kingdom

Sexual assaults under benzodiazepine submission have been described, since use of benzodiazepine enables non consensual sexual activity but rarely fully reported. An accurate evaluation of the phenomenon has seemed interesting. Files of 23 adult males and females examined at the Emergency Forensic Unit of an University Teaching Hospital near Paris were reviewed. All the victims had complained from sexual assault under drug submission, in the years 1996 and 1997. A complete examination for sexual assault was realised linked to clinical examination of drug intoxication. Every victim of rape under drug submission was sampled for urine screening (mean delay of 17.5 h after sexual assault) and blood alcohol level quantification. Urine was screened for benzodiazepines, cocaine, opiates and cannabinoids with qualitative immunochromatographic test. Traumatic lesions of sexual penetration were retrieved in 10 victims and sperm in 5. Clinical signs of benzodiazepine intoxication were retrieved in 12 out of 23 victims. Urine benzodiazepine screening was positive, over the cut-off values (300 ng/mL)when sampled less than 20 h after the facts. In 6 out of 23 victims, drugs of abuse and alcohol were associated to benzodiazepines. A reinforced attention can be brought to the rape under drug submission including the need of a proper examination and samplings shortly after the alleged facts to ascertain the diagnosis and to help the victim facing the Justice inquiry.

Topics: Adolescent; Adult; Anti-Anxiety Agents; Benzodiazepines; Cocaine; Dronabinol; Estazolam; Female; Flunitrazepam; Humans; Hypnotics and Sedatives; Immunoassay; Lorazepam; Male; Morphine; Narcotics; Nitrazepam; Paris; Rape; Retrospective Studies; Substance-Related Disorders; Temazepam; Time Factors; Triazolam

Besides modern virus-screening methods, the avoidance of transfusion transmission of viral diseases is based on the best possible selection of healthy donors. Unfortunately, most of the relevant behavior-related risk factors are not accessible to objective verification. Drug screening can be used to validate a defined section of donor statements. It may be assumed that donors who conceal drug consumption may also conceal other relevant risk factors.. Hair and urine samples from 186 young potential donors who denied having consumed drugs were investigated by gas chromatography with mass selective detection and a urine fluorescence polarization immunoassay for cannabinoids, amphetamine and amphetamine derivatives, cocaine, and opiates.. Ten potential donors with 14 positive results on hair and urine analyses (6x cannabinoids, 4x cocaine, 1x opiates, 3x dihydrocodeine) could be identified in the population investigated.. The donor history is not adequate for identifying potential donors with risk factors. Deliberately false statements concerning risk factors are a clear breach of trust between the blood bank and potential donors. These unreliable donors represent an incalculable risk for the transfusion recipient. Therefore, it is appropriate to validate donor statements about drug consumption by random hair and urine analyses and to exclude from the donor pool all persons revealed as drug users.

Topics: Adolescent; Adult; Amphetamines; Blood Donors; Cannabinoids; Cocaine; Communicable Diseases; Deception; Female; Germany; Hair; Humans; Male; Mass Screening; Medical History Taking; Morphine; Risk Factors; Substance Abuse Detection; Substance-Related Disorders; Surveys and Questionnaires; Truth Disclosure; Urine

An analytical method for the determination of heroin, 6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine, and cocaethylene in human hair using gas chromatography-tandem mass spectrometry is presented. The analytes were extracted from finely cut hair with methanol at 56 degrees C for 18 h in the presence of nalorphine as the internal standard. After the incubation, methanol was evaporated to dryness, and all the analytes, except heroin, cocaine, and cocaethylene, were converted to their trimethylsilyl derivatives. The reaction products were identified and quantitated using product ions formed from the parent ions by collision-induced dissociation in the ion-trap mass spectrometer. This method provided excellent sensitivity and specificity for analytes at the concentrations usually found in the keratin matrix.

Topics: Cocaine; Codeine; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Humans; Indicators and Reagents; Morphine; Morphine Derivatives; Narcotics; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Trimethylsilyl Compounds

A simple, but sensitive and specific, high-performance liquid chromatographic assay for cocaine, cocaethylene, and benzoylecgonine is described. Using direct fluorometric detection, the procedure is particularly interesting for the routine analysis of human hair samples. In the sample preparation part, the hair samples are cut and washed and two internal standards with close structural resemblance to benzoylecgonine and cocaine as well as to cocaethylene are added. Subsequently, the hair samples are homogenized, hydrolyzed overnight in a 0.1 M HCl solution at 56 degrees C, and extracted on IST Confirm HCX solid-phase extraction columns. Chromatographic separation is achieved on a narrow-bore Hypersil BDS C18 column (125 x 2.1 mm, 3 microns) by gradient elution with an ammonium acetate buffer-methanol/acetonitrile mixture. For the fluorometric detection, excitation and emission wavelengths of 242 and 315 nm, respectively, are used. This analysis protocol affords a method of high sensitivity and specificity which has been fully evaluated and validated. The data presented show good accuracy and linearity with excellent reproducibility and recovery. Because unequivocal identity confirmation is mandatory in forensic applications, an extension of the analysis protocol was accomplished toward mass spectrometric detection. We succeeded in a simple methodological transfer from LC/FL to LC/ESI-MS/MS, thus providing two complementary approaches after a single, common sample-processing step. Hair samples from 29 fatalities, all known drug users and suspected victims from a drug overdose, were analyzed in this way. Of the investigated samples, 12 were positive and the concentrations found range from 0.98 to 938 ng/mg of hair for cocaine and from 1.45 to 388 ng/mg of hair for benzoylecgonine. Traces of cocaethylene were also found in two of the hair samples. The results obtained with LC/ESI-MS/MS were in close agreement with those obtained with LC/FL, positively confirming the isolates' identity and structure by means of the resulting MS/MS spectra.

Topics: Chromatography, High Pressure Liquid; Cocaine; Hair; Humans; Mass Spectrometry; Reproducibility of Results; Spectrometry, Fluorescence; Substance-Related Disorders

To determine the prevalence of recent cocaine use and the accuracy of self-reported use, the results of a urine assay for the major cocaine metabolite benzoylecgonine were compared with self-reported cocaine use in an inner-city prenatal population offered routine voluntary urine toxicology screening at the time of registration for prenatal care. During a 1-year period, 6866 women registered for prenatal care and 5200 (76%) consented to urine assays for cocaine metabolites. Of the women consenting to urine assays, 253 (5%) had positive assays for benzoylecgonine. Women with positive assays were significantly more likely than those with negative assays to be older (mean [SD] 27 [5] versus 23 [6] years), black, single, and unemployed. In addition, women with positive assays were significantly more likely to be multiparous, report > two sexual partners in the previous year, and acknowledge a history of a sexually transmitted disease (STD). Forty-seven percent of women with positive assays acknowledged cocaine use in the 6 months prior to sampling. Women with positive assays who denied cocaine use were significantly more likely than those who admitted use to be younger (mean [SD] 26 [5] versus 28 [4] years), to report > or = two sexual partners in the past year, and acknowledge a history of an STD. This analysis revealed a poor correlation between self-reported cocaine use and the results of urine assays for cocaine metabolites among women seeking prenatal care in an inner-city institution.

Topics: Cocaine; Female; Health Behavior; Humans; Pregnancy; Prenatal Care; Prevalence; Self Disclosure; Substance-Related Disorders; Surveys and Questionnaires; United States; Urban Population

Substance abuse worsens the course of schizophrenia and significantly impairs the relationship between the patient and the health care team. Recent advances in laboratory studies of substance abuse and the pharmacology of schizophrenia open up new possibilities for pharmacotherapy of substance abuse in schizophrenia patients. D1 dopaminergic receptor agonists may directly block the drive for stimulant use. D2 dopaminergic receptor antagonists may indirectly block the drive for stimulant and nicotine use, while opioid antagonists appear to reduce the drive to use alcohol. New generations of neuroleptics with serotonin (5-HT2) receptor antagonism and/or 5-HT1A agonist activity may reduce substance abuse in schizophrenia patients who self-medicate negative symptoms or neuroleptic side effects. Pharmacotherapy efficacy may be enhanced by adding contingency management, social skills training, and other manualized programs. Tables are provided of potentially useful medications. Preliminary results are presented of cocaine-abusing schizophrenia patient treated with desipramine and traditional neuroleptics.

Topics: Alcoholism; Antipsychotic Agents; Cocaine; Flupenthixol; Humans; Imipramine; Marijuana Abuse; Opioid-Related Disorders; Schizophrenia; Self Medication; Substance-Related Disorders; Tobacco Use Disorder

Toxicological investigation of suspected cocaine-related deaths routinely involves the identification of cocaine (COC) and its metabolites including benzoylecgonine (BE) and ecgonine methyl ester (EME) in postmortem specimens. We utilized solid-phase extraction followed by gas chromatography/mass spectrometry for the qualitative and quantitative analysis of cocaine and eight cocaine-related analytes. These analytes included anhydroecgonine methyl ester (AEME), a unique product formed during cocaine smoking, and cocaethylene (CE), formed by transesterification of cocaine in the presence of ethanol. Thirteen pairs of postmortem heart blood and urine specimens were analyzed from cases of death due to acute cocaine intoxication, multiple drug intoxication, or other non-drug related causes. COC, EME, and BE were detected in all specimens. The range of concentrations in blood were: COC, 23-2088 ng/mL; BE, 215-9195 ng/mL; and EME, 220-7275 ng/ mL. AEME was identified in 2 blood and 10 urine specimens, and CE was identified in 1 blood specimen and 4 urine specimens. The identification of AEME in the specimens indicated that "crack" cocaine had been smoked, and the presence of CE indicated co-administration of cocaine and ethanol. The presence of these unique cocaine analysis in postmortem specimens provides valuable information regarding the cause and manner of death.

Topics: Cocaine; Crack Cocaine; Gas Chromatography-Mass Spectrometry; Humans; Narcotics; Postmortem Changes; Smoking; Substance-Related Disorders

We have become aware of several commercial products that, when orally ingested, will purportedly not only eliminate "toxins" from a person's system, but will also correct any urinary imbalances caused by excessive water consumption.. Unblinded study of one volunteer subject, tested weekly x 4 for 24-hour urine elimination of test drug under conditions of control, control plus 1200 mL water, Quick Flush', and Eliminator.. Each of the treatment protocols studied caused reductions of drug or metabolite concentrations as measured by gas chromatography-mass spectrometry in urine specimens collected up to 24 hours after ingestion of amphetamine, 9-carboxy-11-nor-delta-9-THC, benzoylecgonine, or codeine, yet the radioimmunoassay screening results demonstrated very little effect. Water alone was approximately as effective as the two commercial products in reducing the metabolite level. None of the treatment protocols employed in this study altered urinary pH, specific gravity, or creatinine concentration outside the normally accepted physiological range.. Attempts to conceal drug abuse by water dilution are most likely to play a substantial role when concentrations are at or near the detection threshold for a particular assay such as the terminal stages of drug eliminations.

Topics: Amphetamine; Cocaine; Codeine; Creatinine; Dronabinol; Drug and Narcotic Control; Gas Chromatography-Mass Spectrometry; Humans; Illicit Drugs; Male; Radioimmunoassay; Substance Abuse Detection; Substance-Related Disorders; Urinalysis

Immunoassay has been established with polyclonal or monoclonal antibody even for a low molecular weight compound which has no antigenicity. In spite of the cross-reactivities of an antibody and also the difficulty in identification of the compound, an immunoassay is a useful method of choice for the detection of the compound in biological fluids because of the pretreatment simplicity and ability to treat many samples in a short time. Therefore, immunoassay has been established as a sensitive analytical and screening method for use in forensic sciences. In our laboratory, a radioimmunoassay (RIA) and an enzyme immunoassay (EIA) for phenobarbital, and enzyme-linked immunosorbent assays (ELISA) and latex agglutination inhibition reaction tests (LAIRT) for methamphetamine, benzoylecgonine and morphine have been established. These assays are described in addition to the two commercially available immunoassay kits, enzyme multiplied immunoassay technique (EMIT; Syva Co., USA) and Triage Biosite Piagnostics, Inc, USA.

Topics: Central Nervous System Agents; Cocaine; Enzyme-Linked Immunosorbent Assay; Forensic Medicine; Humans; Latex Fixation Tests; Methamphetamine; Morphine; Phenobarbital; Radioimmunoassay; Sensitivity and Specificity; Substance-Related Disorders

Topics: Amniotic Fluid; Case-Control Studies; Cocaine; Female; Gastric Juice; Humans; Infant, Newborn; Meconium; Neonatal Screening; Pregnancy; Pregnancy Complications; Substance Abuse Detection; Substance-Related Disorders; Urinalysis

The interaction between cocaine (COC) and ethyl alcohol (ALC) was investigated in ALC-naive and ALC-pretreated rats. In each group, COC (30 mg/kg ip) was administered 15 min after administration of ALC (3 g/kg, by gavage) or normal saline (NS), in a balanced cross-over experimental design. Cocaethylene (CE) was detected only in the rat plasma when ALC was administered with COC. In the ALC-naive rats, COC area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cpmax) were significantly higher after administration of COC+ALC compared with after administration of COC+NS. However, COC half-life (t1/2) was not different after the two treatments, indicating that the higher COC Cpmax and AUC after COC+ALC primarily resulted from enhanced COC absorption. In the ALC-pretreated rats, COC AUC, Cpmax, and t1/2 were not different after administration of COC+ALC or COC+NS. However, COC t1/2 in the ALC-pretreated rats after COC+ALC and COC+NS were significantly longer than the corresponding COC t1/2 in the ALC-naive rats. This indicates that repeated ALC exposure significantly slows the rate of COC elimination. In the ALC-pretreated rats, CE AUC was significantly larger, and t1/2 was significantly longer than CE AUC and t1/2 in the ALC-naive rats. This indicates that previous ALC exposure inhibits CE elimination and may increase the fraction of COC dose metabolized to CE. Benzoylecgonine formation was significantly reduced, and its t1/2 was significantly prolonged after administration of COC+ALC in the ALC-naive and the ALC-pretreated rats. These results suggest that the combined abuse of COC and ALC leads to higher plasma COC concentrations that can lead to augmentation of cocaine effects in addition to the COC-like effects of CE. Also, repeated use of ALC slows the rate of COC elimination after administration of COC either alone or in combination with ALC, resulting in higher and prolonged COC plasma concentrations that can potentiate COC effects and toxicities. This higher COC concentrations in addition to the formation of CE are, at least partially, responsible for the serious consequences associated with the combined abuse of COC and ALC.

Topics: Alcoholism; Animals; Cocaine; Cross-Over Studies; Drug Interactions; Ethanol; Male; Rats; Rats, Wistar; Substance-Related Disorders

An enzyme-linked immunosorbent assay (ELISA) and a latex agglutination inhibition reaction test (LAIRT) for cocaine and benzoylecgonine have been established. In ELISA with polystyrene microtiter wells coated with anti-benzoylecgonine antibody and alkaline phosphatase (ALP)-labeled benzoylecgonine, the activity of antibody-bound ALP was measured with the enzyme cycling method. The range of benzoylecgonine measurable by ELISA was 12 pg-25 ng/well; the analysis time for 96 wells was 90 min. In LAIRT, the agglutination reaction with anti-benzoylecgonine antibody-coated latex and benzoylecgonine-rabbit serum albumin (RSA) conjugate-coated latex was inhibited by 0.1 mu g benzoylecgonine/ml urine; the analysis time for six samples on one glass slide was 20 min. The urine samples of 47 abusers were analyzed by ELISA and LAIRT. From the comparison with results of the enzyme-multiplied immunoassay technique (EMIT) and gas chromatography-mass spectrometry (GC-MS), it was clarified that both ELISA and LAIRT were suitable for the screening method of urine samples.

Topics: Animals; Cocaine; Enzyme Multiplied Immunoassay Technique; Enzyme-Linked Immunosorbent Assay; Gas Chromatography-Mass Spectrometry; Humans; Latex Fixation Tests; Rabbits; Substance-Related Disorders

We evaluated the Abuscreen ONTRAK assay for cocaine metabolites, a rapid immunoassay for the detection of cocaine metabolites in a pediatric emergency department (ED) setting. The ONTRAK uses a cutoff point of 300 micrograms/L for benzoylecgonine (BEC), cocaine's major urinary metabolite. One hundred and thirty-two urine specimens obtained from infants, children, and adolescents whose clinical findings warranted toxicology screening were evaluated. The ONTRAK identified all 15 specimens with BEC values of 300 micrograms/L, but did not detect seven additional specimens positive for cocaine metabolites at concentrations less than 300 micrograms/L. One third of the positive specimens for cocaine metabolite identified by fluorescent polarization immunoassay (FPIA), cutoff point set at 80 micrograms/L, and confirmed by gas chromatography/mass spectrometry (GUMS), cutoff point 50 micrograms/L, were not detected by the ONTRAK. These false negative specimens were seen exclusively in young children, whose concentration of cocaine metabolite was less than the ONTRAK's cutoff value. The test was sensitive to drug concentration at or around the stated cutoff values. The ONTRAK test for cocaine metabolites, although both a sensitive and specific screening test for adolescents who smoke or snort cocaine, lacks the sensitivity to be a useful screening too[ for detecting cocaine metabolites in young children. Limitations of currently performed toxicology screening tests (ie, stated cutoff levels) may cause emergency physicians to miss most young children whose symptoms may he related to cocaine exposure.

Topics: Adolescent; Child; Child, Preschool; Cocaine; Emergency Service, Hospital; Evaluation Studies as Topic; Fluorescence Polarization Immunoassay; Gas Chromatography-Mass Spectrometry; Humans; Infant; Latex Fixation Tests; Prospective Studies; Substance Abuse Detection; Substance-Related Disorders

To assess differences in the binding of cocaine, cocaethylene, and benzoylecgonine among pigmented and senile white hairs of the graying human cocaine abuser.. A sheath of graying hair in the region around the apex of the head was gathered between the thumb and index finger then cut and removed about 2 mm proximal to the scalp. The graying hair was divided into pigmented and senile white of equal weights and lengths and then analyzed by gas chromatography/mass spectrometry chemical ionization. Twenty-nine such pairs were analyzed.. Male cocaine abusers, ages 33-55 years hospitalized for substance abuse. Informed consent was obtained and confidentiality assured.. Concentrations of cocaine, cocaethylene and benzoylecgonine in ng were assessed for each of 29 paired hair samples by gas chromatography/mass spectrometry chemical ionization.. There were statistically significant differences between pigmented and senile white sections of paired samples. Cocaine (ng/mg hair, mean +/- SD) was 31.5 +/- 30.2 for pigmented hair vs 14.9 +/- 19.8 for senile white portions; (p < 0.0001). Cocaethylene (ng/mg hair, mean +/- SD) 3.22 +/- 5.0 (pigmented) vs 0.52 +/- 0.88 (senile white); (p < 0.0016). Benzoylecgonine (ng/mg hair, mean +/- SD) 5.1 +/- 5.3 (pigmented) vs 3.9 +/- 4.8 (senile white); (p < 0.005).. Melaninated pigmented hair seems to bind more cocaine, cocaethylene and benzoylecgonine than white hair in the same subject.

Topics: Adult; Cocaine; Gas Chromatography-Mass Spectrometry; Hair; Humans; Male; Middle Aged; Narcotics; Pigments, Biological; Substance-Related Disorders

To determine the prevalence of cocaine and opiate metabolites in the urine of young urban and suburban children.. Survey.. Urban and suburban emergency departments and private pediatric practices.. A convenience sample of 1469 children between 1 and 60 months of age who required a urinalysis for investigation of the chief complaint.. None.. Urine was screened for benzoylecogonine and opiates using an enzyme-multiplied immunoassay technique and a fluorescence-polarization immunoassay, both with a sensitivity of 50 ng/mL.. Benzoylecogonine was identified in the urine of 45 children (3.1%) (95% CI, 2.2% to 3.9%) and opiates in the urine of 38 children (2.6%) (95% CI, 1.8% to 3.4%). No difference was observed between urban and suburban health care facilities in the percentage of patients whose urine tested positive for benzoylecgonine (29 of 1011 vs 16 of 458, P = .6) or opiates (28 of 1011 vs 10 of 458, P = .6).. Exposure to illicit drugs, as reflected by urinary metabolites, is similar for urban and suburban children.

Topics: Child, Preschool; Cocaine; Humans; Illicit Drugs; Infant; Narcotics; Prevalence; Substance-Related Disorders; Suburban Health; United States; Urban Health

Topics: Cocaine; Emergency Service, Hospital; Humans; Office Visits; Substance Abuse Detection; Substance-Related Disorders

Cocaine intoxication can lead to fatal cardiovascular and cerebrovascular events. In addition, the neurobehavioral effects of cocaine may increase the likelihood that a user will receive violent fatal injuries. Since New York City is a center for the importation and distribution of cocaine, we sought to determine the extent of cocaine use among city residents with fatal injuries.. Among a total of 14,843 residents of New York City who received fatal injuries from 1990 through 1992, we determined the proportion who used cocaine shortly before their deaths. We also determined the population-based rates of fatal injuries that were known to follow cocaine use and the proportion of all deaths of New York City residents that was represented by these cases for each demographic stratum. For adults 15 to 44 years of age, fatal injury after cocaine use was ranked with other causes of death as though it was a separate cause.. Cocaine use, as measured by the detection of the metabolite benzoylecgonine in urine or blood, was found in 26.7 percent of all New York City residents receiving fatal injuries; free cocaine was detected in 18.3 percent. Approximately one third of deaths after cocaine use were the result of drug intoxication, but two thirds involved traumatic injuries resulting from homicides, suicides, traffic accidents, and falls. If fatal injury after cocaine use was considered as a separate cause of death, it would rank among the five leading causes of death among those 15 to 44 years of age in New York City.. Fatal injuries among cocaine users account for a substantial proportion of all deaths among young adults in New York City.

Topics: Adolescent; Adult; Cause of Death; Cocaine; Ethanol; Female; Humans; Male; New York City; Substance-Related Disorders; Wounds and Injuries

When blood or urine is unavailable, postmortem meconium or stool from infants or stillbirths can be used to detect drugs-of-abuse, thus providing datum in assessing drug-abuse exposure. Two case reports illustrate how drugs-of-abuse findings in post-mortem specimens were used to substantiate exposure prior to death or a history of maternal drug abuse. The first, a congenital hydrocephalus, born to a non-drug abusing mother, expired at the age of 41 days, had opiates in the stool by screening method, enzyme multiplied immunoassay technique, confirmed by gas chromatographic/mass spectrometric (GC/MS) analysis. Investigation revealed that morphine had been administered for three days prior to death. The second was a stillbirth infant born to a drug abuser. Almost equal amounts of benzoylecgonine were found in different bowel segments, a finding consistent with admitted cocaine use throughout pregnancy.

Topics: Adult; Cocaine; Feces; Female; Fetal Death; Humans; Hydrocephalus; Infant; Infant, Newborn; Male; Meconium; Morphine; Pregnancy; Substance-Related Disorders

Intrauterine brain growth retardation is the most common brain abnormality in infants of cocaine-abusing mothers. We report a cross-sectional study of "at-risk" pregnancies with 34 infants born to mothers urine positive for cocaine at delivery compared to 33 infants born to urine-negative mothers from the same clinic. Degree of cocaine exposure was assessed by radioimmunoassay of combined cocaine and benzoylecgonine (BE) levels in neonatal hair samples. Twenty-eight neonates were hair-positive for BE (mean 2507.40 +/- 1248.88 ng/g hair; range 716 to 5440 ng/g) and differed significantly from the control infants (n = 33) in head circumference and head growth percentiles. A negative correlation approaching significance was found between mean BE and head circumference (r = -.36; p < .06) in the group of newborns with hair positive for BE (n = 28). The study demonstrates for the first time head growth abnormalities in association with levels of cocaine exposure.

Topics: Adult; Cocaine; Cross-Sectional Studies; Female; Hair; Head; Humans; Infant, Newborn; Male; Maternal Behavior; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Substance-Related Disorders

This work studies the distribution of cocaine and heroin metabolites in hair and urine of living polidrug abusers. Cocaine, benzoylecgonine (BEG), ecgonine methyl ester (EME), morphine, codeine and 6-monoacetylmorphine (6-MAM) were simultaneously extracted and analyzed by GC/MS in SIM mode. The results obtained show a different distribution of heroin and cocaine metabolites in urine and hair. In urine, we generally find BEG and EME for cocaine abuse, and morphine for heroin abuse. In hair, we detect cocaine and MAM as major metabolites for cocaine and heroin abuse, respectively.

Topics: Cocaine; Codeine; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Humans; Morphine; Morphine Derivatives; Narcotics; Substance-Related Disorders

We evaluated the EZ-SCREEN Test Kit (Editek, Inc., Burlington, NC), a point-of-care screening test for the presence of cocaine metabolite (benzoylecgonine; BE), cannabinoids (tetrahydrocannabinol; THC) and opiates in urine. Patient specimens (n = 34) were tested in the laboratory using both Abbott Laboratories ADx (ADx) and EZ-SCREEN (EZS-LAB), and by the nursing staff of an inpatient substance abuse treatment program using the EZ-SCREEN (EZS-RN). We found comparable analytical efficiency between methods used in the laboratory (> 95% for all three analytes with EZS-LAB and ADx) but lower efficiency for THC and BE with point-of-care testing (approximately 82% for EZS-RN). Efficiency for EZS-RN opiates was 100%. We conclude that the EZ-SCREEN Test Kit may not be suitable for use in a busy clinical setting, unless specific measures are taken to insure the accuracy of point-of-care testing (e.g., minimal interruption or distraction, careful training). We recommend that prior to routine use of point-of-care testing products they be evaluated under normal working conditions with personnel who will eventually be required to perform routine testing.

Topics: Cocaine; Dronabinol; Humans; Marijuana Abuse; Narcotics; Nursing Assessment; Opioid-Related Disorders; Patient Care Team; Point-of-Care Systems; Reagent Kits, Diagnostic; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders

Urinalysis of benzoylecgonine (BE) concentrations is a primary outcome measure for evaluating medications for treating cocaine addiction. Using simulated BE data from a set of simple clinical models, the advantages of quantitative versus qualitative urinalysis were evaluated, as well as the advantages of once-weekly versus thrice-weekly sampling schedules. A 60 percent reduction in cocaine use, either in daily amount or in weekly frequency, was considered clinically significant. Quantitative urinalysis can detect reductions in both amount and frequency, whereas qualitative urinalysis can detect only a decrease in frequency. For quantitative urinalysis, changes are more easily detected when urine is collected three times a week than when it is collected once a week. For qualitative urinalysis, the majority rule analysis for a thrice-weekly sampling schedule yields an artificially high estimate of the percentage of positive samples, whereas a once-weekly schedule gives a highly variable estimate.

Topics: Cocaine; Humans; Narcotics; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

There has been an increasing use of cocaine in North America among women of reproductive age. The potential effects of cocaine on the fetus have raised serious concerns about the health of large numbers of children exposed in utero to the drug. Using neonatal hair and urine tests for benzoylegconine (BE), we quantified the incidence of fetal exposure to cocaine among 600 babies born in 3 nurseries in Toronto from 1990-91. A total of 37 babies (6.25%) tested positive for cocaine exposure by either hair test, urine test, or both. The hair test detected 33 cases and failed to identify 4 babies who had low urine concentrations of BE. The urine test failed to identify 76% of the cases. In downtown Toronto, the overall rate of fetal exposure to cocaine was 12.5% (25/200), significantly higher than in the 2 suburban nurseries (3%; 12/400). Babies are born with hair which has grown during the last trimester of pregnancy; hence, our analysis identifies women who have used cocaine long after they became aware of pregnancy. Our figures translate to more than 5,000 babies annually in the greater Toronto area who are cared for postnatally by mothers regularly using cocaine. Because history and urine testing during delivery fail to identify the majority of these cases, most of these children are not likely to receive the appropriate medical and social services and follow-up.

Topics: Adolescent; Adult; Canada; Cocaine; Female; Fetus; Hair; Humans; Infant, Newborn; Middle Aged; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; Substance-Related Disorders

In the later stages after intake, the important markers of cocaine abuse are its main metabolites in urine, benzoylecgonine and ecgonine methyl ester. The efficiency of the extraction of amphoteric benzoylecgonine together with cocaine from aqueous media by means of various solvents at various pH values and by means of a mixed solid phase was tested. The extraction of benzoylecgonine with diethyl ether is not efficient, whereas chloroform, dichloromethane or mixed solid-phase extraction give satisfactory results. The analytical strategy for the general chromatographic screening and identification of unknown drugs in biological samples based on diethyl ether extraction was modified to permit the sensitive detection of cocaine abuse also on the basis of benzoylecgonine. A complementary high-performance liquid chromatographic method with photodiode-array detection after solid-phase extraction was introduced for specific confirmation and determination of cocaine and benzoylecgonine.

Topics: Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Cocaine; Humans; Hydrogen-Ion Concentration; Narcotics; Solvents; Spectrophotometry, Ultraviolet; Substance Abuse Detection; Substance-Related Disorders

In this preliminary study, the level of Benzoyl Ecgonine (BE), a metabolite of cocaine, was compared in urine and buccal mucosal transudate collected by a salt impregnated swab in volunteers admitted for cocaine use. The presence of BE (specificity) was verified by the SYVA EMIT method and the urine and transudate levels measured using the Sigma ELISA methods. Results were confirmed using Gas Chromatography/Mass Spectrometry. In all, 44 patients volunteered, and BE in urine or saliva confirmed that each volunteer had in fact used cocaine. The salt-impregnated swab permitted detection of cocaine or its derivative in 27 of the 44 cases. The paper discusses the possibility of using buccal mucosal transudate as collected by salt-impregnated buccal swab as a minimally-invasive measure of cocaine use. This method would allow positive confirmation by a witness that the sample came from a given patient.

Topics: Adult; Cocaine; Enzyme-Linked Immunosorbent Assay; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Metabolic Clearance Rate; Mouth Mucosa; Narcotics; Pilot Projects; Substance Abuse Detection; Substance-Related Disorders

A large scale drug screening study was done to determine the prevalence of drug use in a large metropolitan, obstetric population. Meconium and first voided urine, as well as maternal urine were collected from 423 consecutive deliveries. Urine samples and methanolic extracts of meconium were initially screened by Enzyme Multiplied Immunoassay Technique (EMIT) and then confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). Analysis of cocaine metabolite as benzoylecogonine, cannabinoid as carboxy-THC, codeine, morphine and methadone were included in the study. The positive rate for benzoylecgonine was virtually identical for meconium, maternal urine and neonatal urine (12%). Analysis of meconium was found to be more reliable than analysis of maternal or neonatal urine for the detection of benzoylecgonine. Meconium did not appear to offer an advantage over maternal or neonatal urine for detection of cannabinoid, codeine, morphine, or methadone.

Topics: Adult; Cocaine; Dronabinol; Female; Gas Chromatography-Mass Spectrometry; Humans; Illicit Drugs; Immunoassay; Infant, Newborn; Meconium; Methadone; Narcotics; New York City; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prevalence; Reproducibility of Results; Substance Abuse Detection; Substance-Related Disorders

To compare radioimmunoassay of postpartum maternal hair samples with a structured maternal interview for the detection of cocaine use during pregnancy.. Radioimmunoassay of hair samples obtained postpartum was compared with self-report of cocaine use obtained by confidential, structured interviews of 405 postpartum women.. Cocaine or benzoylecgonine was detected in the hair samples of 129 of the 148 women (87%) who reported using cocaine at least once during pregnancy. Thirty-six of 257 women (14%) who reported that they had used no cocaine during pregnancy had positive hair tests. Positive hair assay with negative self-report was significantly more common among women who were unmarried (P = .001), African-American (P < .001), and multiparous (P = .035).. Hair analysis is a valuable complement to maternal self-report by interview. The methods used together provide a useful clinical and research technique yielding a comprehensive estimate of gestational cocaine exposure. Either method alone may result in misclassification of gestational cocaine exposure.

Topics: Adult; Black or African American; Cocaine; Female; Hair; Humans; Interviews as Topic; Marital Status; Parity; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Radioimmunoassay; Self Disclosure; Substance Abuse Detection; Substance-Related Disorders; White People

The last decade an increase has been seen in drug smuggling. Body-packing and body-stuffing are the terms used for intracorporeal concealment of illicit drugs (mainly cocaine and heroine, but sometimes also amphetamines and cannabinoids). These body-packets are especially prone to rupture. In order to avoid systemic cocaine toxicity, which can involve nearly every organ and therefore nearly every subspecialty of medicine urgent diagnosis is necessary. Obtaining a detailed history remains crucial. Further clues to diagnosis are given by the urinary drug concentrations and the benzoylecgonine/cocaine ratio in urine. Plain abdominal films, CT and contrast studies of the bowel can be helpful in identifying the package but are of limited value. In addition to activated charcoal, polyethylene glycol-electrolyte lavage solution, enteral feeding and laxatives (not paraffin) can be used to eliminate the body-package by enhancing bowel transit. Alkalinisation of gastric fluids enhances hydrolysis to cocaine's major inactive metabolite benzoylecgonine. If the package fails to progress through the gut or if mechanical obstruction occurs surgical removal is indicated. In no way endoscopic removal of the package should be attempted. Systemic symptoms should be treated by blocking the sympathetic overreactivity; this can be done with diazepam (Valium), labetalol (Trandate) or esmolol. Flumazenil (Anexate), lidocaine (Xylocaine) and pure beta-blockers like propranolol (Inderal) are to be avoided.

Topics: Adult; Cocaine; Coma; Critical Care; Female; Humans; Liver Function Tests; Pancreatic Function Tests; Substance-Related Disorders

To assess the value of the current NIDA cutoff concentrations for screening assays that detect urinary cocaine metabolites and phencyclidine (PCP), we collected data on concentrations of these drugs in newborns and patients admitted to the Los Angeles County + University of Southern California Medical Center from July 1, 1991, to December 31, 1991. Less than 2% of the patients were positive for PCP. However, 16.5% of the newborns and 25.1% of the remaining age groups tested positive for cocaine metabolites. Among specimens that tested negative with the screening assays, approximately 3% (182 specimens, with 15 from newborns) clearly contained detectable amounts (between 50 and less than 300 ng/mL) of benzoylecgonine by GC/MS, while less than 0.6% had detectable amounts (10-25 ng/mL) of PCP. The mothers of 7 of the 15 newborns also had detectable benzoylecgonine at various concentrations. This indicates that a lower screening cutoff concentration may be desirable for cocaine metabolites in hospitalized patients. Among those patients positive for cocaine metabolites or PCP, most were males between 20 and 39 years old. The urine drug concentrations in this population were 4-300 times greater than the cutoff concentrations for the screening assays.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cocaine; Female; Gas Chromatography-Mass Spectrometry; Hospitals, Teaching; Humans; Infant; Infant, Newborn; Male; Middle Aged; Phencyclidine; Substance Abuse Detection; Substance-Related Disorders; Urban Population

A new method was developed for the simultaneous detection and quantitation of 6-acetyl-morphine (MAM), amphetamine, benzoylecgonine (BZE), cocaine, codeine, dihydrocodeine, EDDP (methadone metabolite), methadone and morphine in hair. The hair samples were washed, cut into 2-cm segments, pulverized, incubated with phosphate buffer and beta-glucuronidase/aryl-sulfatase. After solid phase extraction and derivatization with pentafluoropropionic anhydride/pentafluoropropanol, the drugs were identified and measured by gas chromatography/mass spectrometry using their deuterated analogues as internal standards. The method is reproducible with detection limits under 0.1 ng/mg hair for almost all substances tested. Fifteen hair samples from five subjects of a methadone treatment program were collected in a 6-month period. The hair samples were segmented and examined for methadone, its main metabolite EDDP, and drugs of abuse. Of the 96 segments analysed, 95% were positive for methadone (mean value, 10.9 ng/mg), 76% for the metabolite EDDP (mean value, 1.2 ng/mg), 69% for opiates (mean values, MAM, 7.3 ng/mg; morphine, 2.9 ng/mg; codeine, 1.0 ng/mg) and 43% for cocaine (mean values, cocaine, 2.6 ng/mg; BZE, 1.1 ng/mg). A correlation of 0.63 was found between administered methadone dosages and concentrations measured by hair analysis. Further investigation is needed to clarify interindividual differences.

Topics: Adult; Amphetamine; Calibration; Cocaine; Codeine; Female; Gas Chromatography-Mass Spectrometry; Hair; Humans; Illicit Drugs; Male; Methadone; Morphine; Morphine Derivatives; Reproducibility of Results; Substance Abuse Detection; Substance-Related Disorders

Cocaine and its metabolites, benzoylecgonine (BZE) and ecgonine methylester (EME), were found in hair samples from ancient Peruvian coca-leaf chewers dating back to AD 1000. Hair was analyzed by gas chromatography/mass spectrometry (GC/MS) to quantitate the concentrations. The two metabolites were found in higher concentration than the parent drug. The metabolite levels appear to be below that of modern cocaine abusers. Gender does not appear to be a factor in the incorporation of drug into hair.

Topics: Adult; Cocaine; Female; Hair; History, Ancient; Humans; Male; Middle Aged; Mummies; Peru; Substance Abuse Detection; Substance-Related Disorders

Previous studies have shown that cocaine consumption alters the normal immune functions of animals. Several epidemiologic studies have indicated an association between cocaine consumption and an increased risk for AIDS. In the present studies, unstimulated peripheral blood mononuclear cells (PBMC) isolated from 8 healthy, human immunodeficiency virus (HIV) type 1-seronegative volunteers were exposed to cocaine or one of its by-products, in vitro, at concentrations compatible with blood levels found during clinical abuse of cocaine. PBMC treated with cocaine had significantly increased levels of HIV-1 replication after infection in vitro compared with untreated PBMC. The major cocaine by-product, benzoylecgonine, did not appear to exert any significant potentiating effect on HIV-1 replication. Cocaine or its by-product did not significantly increase HIV-1 replication in persistently HIV-1-infected T lymphocytic or monocytoid cell lines. These data indicate that exposure of PBMC but not chronically HIV-1-infected cell lines to cocaine can result in increased HIV-1 replication.

Topics: Adjuvants, Immunologic; Cells, Cultured; Cocaine; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Monocytes; Substance-Related Disorders; T-Lymphocytes; Virus Replication

A confirmation procedure for the analysis of cocaine, benzoylecgonine, ecgonine, and phencyclidine (PCP) in human hair using tandem mass spectrometry has been developed. This procedure requires no solvent extraction and thus can examine the metabolites of drugs such as cocaine. Hairs from six cocaine users were examined and the amount of cocaine and its ratio to the metabolites was not correlated to the reported use pattern. Only PCP was detected in the hair from a PCP user, no metabolites were found. In passive exposure experiments, hair was found to tightly absorb PCP from aqueous solutions, which mimics the incorporation of PCP by the body. These results indicate that drugs may be absorbed onto the hair of nonusers and become tightly bound.

Topics: Cocaine; Hair; Humans; Mass Spectrometry; Phencyclidine; Substance-Related Disorders

To determine whether analysis of amniotic fluid (AF) using solid-phase extraction and high-performance liquid chromatography is useful in detecting fetal exposure to cocaine and its metabolites.. Amniotic fluid and urine samples were obtained from 23 subjects with documented cocaine abuse during pregnancy and five subjects without a history of cocaine abuse. Urine samples were also collected from all newborns. Urine samples were screened using conventional immunoassay techniques and confirmed with thin-layer chromatography. Using a modified solid-phase extraction procedure, we removed cocaine and its metabolites from all AF samples and from the newborn urine samples in which the initial screening was positive. Subsequently, we analyzed the extracts with high-performance liquid chromatography.. Cocaine or benzoylecgonine was detected in 74% of AF samples taken from the 23 known cocaine abusers. In these subjects, conventional maternal and neonatal urine toxicology screens were positive in 61 and 35%, respectively. Concentrations in AF ranged from 400 to greater than 5000 ng/mL for benzoylecgonine and from trace to 250 ng/mL for cocaine. Mean benzoylecgonine recovery from AF was significantly greater than from newborn urine (1800 versus 280 ng/mL, respectively; P < .0001).. Analysis of AF appears to be useful in detecting gestational cocaine exposure.

Topics: Amniotic Fluid; Chromatography, High Pressure Liquid; Cocaine; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Urinalysis

A method for simultaneous extraction of cocaine and metabolites benzoylnorecgonine, benzoylecgonine and norcocaine from meconium was developed. The procedure uses solid-phase extraction columns with both cation-exchange and hydrophobic properties after vortex-mixing meconium with methanol. Chromatography utilizes reversed-phase high-performance liquid chromatography with a C18 column and phosphate buffer-acetonitrile as mobile phase. The method is specific and sensitive to 50 ng/g meconium for all compounds. Standard curves are linear from 0.05 to 5.0 micrograms/g (r2 > or = 0.989). Intra-assay coefficients of variation were < or = 6.9%. Meconium from infants exposed to cocaine in utero contained varying combinations of the four drugs.

Topics: Chromatography, High Pressure Liquid; Cocaine; Female; Humans; Infant, Newborn; Meconium; Pregnancy; Substance-Related Disorders

We determined the prevalence of prenatal cocaine use in a racially mixed sample of urban and suburban mothers and correlated its use with maternal demographics and newborn measurements.. Meconium from 621 consecutive newborns delivered at two university-affiliated urban hospitals were assayed for benzoylecgonine. Maternal and infant characteristics were linked anonymously with the results. Statistical analysis included t test, Fisher's exact test, Duncan's multiple range analysis, and analysis of covariance, with a value of p < 0.05 considered significant.. We found that 3.4% of meconium samples had benzoylecgonine levels exceeding 0.1 micrograms/ml. Its presence was statistically correlated with maternal and neonatal characteristics. A nurse's opinion of cocaine use was correct 22% of the time.. Prenatal cocaine use was statistically associated with multiparity, multigravidity, late-onset and clinic-based prenatal care, public assistance, nonwhite race, and low academic achievement. A nurse's opinion was a poor predictor of maternal cocaine use. Cocaine-exposed infants were significantly smaller, and this correlated best with nonwhite background.

Topics: Birth Weight; Cocaine; Female; Humans; Infant, Newborn; Meconium; Nurses; Pregnancy; Pregnancy Complications; Prenatal Care; Prevalence; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Suburban Population; Urban Population

A new solid-phase extraction procedure for the determination of cocaine and benzoylecgonine in amniotic fluid, using high flow co-polymeric sorbents is reported. The recoveries of cocaine and benzoylecgonine within the range 0.1-1 mg/l were 95.7% and 50.3%, respectively. The use of high-flow sorbents allowed the easy extraction of amniotic fluid regardless of sample viscosity or physical nature. The use of these solid-phase columns provided many advantages over the more commonly used solvent extraction, including an increase in extraction speed and efficiency, reduced operator time, reduced solvent use and disposal volumes and exceptional extract quality. Further, the determination of amniotic fluid obtained from pregnant cocaine users may provide important information about handling of cocaine by the fetus at various gestational ages. The procedure was successfully applied to amniotic fluid from suspected cocaine abusers.

Topics: Amniotic Fluid; Chromatography, High Pressure Liquid; Cocaine; Female; Gestational Age; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Substance Abuse Detection; Substance-Related Disorders

Cocaine and its major metabolites are incorporated into hair during the growth of the shaft and stay there for the whole life of the hair. Cocaine crosses the placenta and its metabolites for example Benzoylecgonine (BZ), have been found in neonatal urine, meconium and hair. In order to utilize hair measurements of cocaine as a biological marker of systemic exposure, we conducted both animal and human investigations on the dose response characteristics of this phenomenon. Our data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the clinically used doses. Similarly, a good correlation was observed in animals between maternal dose and fetal hair accumulation.

Topics: Animals; Biomarkers; Cocaine; Dose-Response Relationship, Drug; Female; Fetus; Guinea Pigs; Hair; Humans; Injections, Subcutaneous; Maternal-Fetal Exchange; Pregnancy; Substance Abuse Detection; Substance-Related Disorders

We determined the prevalence of cocaine and cannabinoid exposure among young children presenting to an urban pediatric emergency department without signs or symptoms suggestive of the exposure. The study included 460 children between 1 and 60 months of age in whom urinalysis was required for investigation of routine pediatric complaints. Anonymously and without informed consent, an aliquot of urine was screened for cocaine metabolite (benzoylecgonine) and 11- or delta-9-tetrahydrocannabinol-9 carboxylic acid with the enzyme multiplied immunoassay technique. Positive specimens were rescreened with a radioimmunoassay and confirmed with gas chromatography/mass spectrometry, if a sufficient quantity of urine was available. Benzoylecgonine was identified in 25 patients (5.4%) by both screening techniques. Enough urine was available for confirmatory testing in eight patients, and all eight urine specimens contained benzoylecgonine. Neither 11- nor delta-9-tetrahydrocannabinol-9 carboxylic acid was detected in any patient. We documented the magnitude of the problem of occult passive cocaine exposure in young children living in an urban environment. Such exposure has serious implications for the assessment of outcomes in postnatal follow-up studies of prenatally exposed children as well as potential risks to children living in household environments where occult cocaine exposure occurs.

Topics: Adult; Child of Impaired Parents; Child, Preschool; Cocaine; Dronabinol; Emergency Service, Hospital; Environmental Exposure; Female; Humans; Infant; Infant, Newborn; Male; Marijuana Abuse; Mass Screening; Population Surveillance; Prevalence; Sampling Studies; Substance Abuse Detection; Substance-Related Disorders; Urban Population

This study endeavored to determine the incidence of intrauterine cocaine exposure in a socioeconomically mixed suburban setting. It also assessed the effectiveness of an anonymous questionnaire in eliciting information on maternal use of illicit drugs during pregnancy. Meconium was collected from 500 consecutively born infants and analyzed for the presence of cocaine and its metabolites. An anonymous two-page questionnaire also was distributed to all postpartum mothers. Of the infants' mothers, (73.2%) were covered by some form of insurance (private), whereas 26.8% either had no insurance or were covered by Medicaid (clinic). Fifty-nine (11.8%) babies tested positive for cocaine. The meconium of 6.3% of the babies whose mothers had private insurance tested positive, while the meconium of 26.9% of the babies whose mothers had Medicaid or no insurance tested positive. 316 (63.2%) of the mothers returned a questionnaire. 73% had private insurance and 27% were covered by Medicaid (clinic). Only five mothers with no insurance or covered by Medicaid admitted using cocaine. It appears that neonatal exposure to cocaine may be an even greater problem than previously imagined, particularly in the private population. In addition, anonymous maternal self-reporting forms probably will not be helpful in identifying infants at risk for illicit exposure to drugs.

Topics: Cocaine; Female; Fetus; Humans; Maternal-Fetal Exchange; Meconium; Pregnancy; Pregnancy Complications; Socioeconomic Factors; Substance-Related Disorders; Suburban Population; Surveys and Questionnaires

Cocaine has recently been shown to affect the outcome of pregnancy when taken by pregnant women. The authors measured fetal concentrations of cocaine and benzoylecgonine and reviewed autopsy and historical data for 62 successive infants who died at less than two days of age and were seen at the Los Angeles County Office of the Chief Medical Examiner-Coroner. Of 43 infants without an obvious cause of death at autopsy, cocaine or benzoylecgonine or both were present in 40%. None of the parameters studied predicted which infants would show cocaine or benzoylecgonine. We conclude that cocaine and benzoylecgonine concentrations should be measured on all infants who die at less than two days of age when the cause of death is not evident at gross autopsy.

Topics: Autopsy; Brain Chemistry; Cause of Death; Cocaine; Female; Fetal Death; Humans; Infant, Newborn; Liver; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Substance-Related Disorders

Topics: Adult; Cocaine; Female; Fluoxetine; Heroin Dependence; Humans; Male; Methadone; Substance-Related Disorders

The authors studied the pattern of benzoylecgonine excretion in 35 male veterans who had recently used large amounts of cocaine. Following admission to a drug-free environment, the veterans completed a short structured interview and gave daily urine samples for benzoylecgonine analysis. Eleven (31.4%) patients excreted benzoylecgonine at levels of 300 ng/mL or above for 120 hours or longer after admission. Eight (22.9%) patients whose enzyme-multiplied immunoassay test results were negative subsequently tested positive. These findings corroborate recent case reports of prolonged presence of benzoylecgonine in the urine and have important implications for drug treatment programs.

Topics: Adult; Chromatography, Thin Layer; Cocaine; Hospitalization; Humans; Immunoenzyme Techniques; Male; Psychiatric Status Rating Scales; Substance-Related Disorders; Time Factors

A review of medical examiners' autopsy records revealed that in 1988, 33 residents of Virginia died of acute cocaine intoxication. The subjects were 19 to 45 years old; most were men, used cocaine intravenously, and used other toxic substances with the lethal dose of cocaine.

Topics: Cardiomyopathies; Cocaine; Coronary Disease; Death, Sudden; Ethanol; Female; Heart; Humans; Male; Organ Size; Poisoning; Sex Factors; Substance-Related Disorders; Virginia

Intestinal ischemia induced by cocaine abuse is a rare condition. To this date, only three cases have been described. The diagnosis of bowel ischemia should be suspected whenever a cocaine addict has severe abdominal pain. A pathological examination of the resected bowel segment was performed in one case, and the diagnosis was confirmed microscopically. However, the existence of pathologic alterations of the intestinal vessels was not confirmed. Why the intestinal injury is segmental and whether it is related to the dose ingested, the administration route, or the combination of cocaine with alcohol, caffeine, or marijuana remain unclear. The authors report one fatal case associated with cocaine-alcohol overdose. The postmortem examination demonstrated the existence of segmental intestinal ischemia. Microscopic study failed to demonstrate thrombosis in the mesenteric vessels; however, we found an unusual lesion affecting the arterioles located in the intestinal submucosa of the hemorrhagic areas.

Topics: Adult; Alcoholic Intoxication; Arterioles; Cocaine; Drug Overdose; Ethanol; Humans; Intestine, Small; Ischemia; Male; Substance-Related Disorders

Topics: Cocaine; Humans; Saliva; Substance-Related Disorders

Using Syva EMIT reagents and a Cobas-Bio centrifugal analyser we have developed a cost-effective assay for the detection in urine of benzoylecgonine, one of the main metabolites of cocaine. With this method up to 2470 samples can be assayed with a single 100-test EMIT Kit while maintaining acceptable precision. A mean CV of 7.0% was obtained for the concentration range 240-620 micrograms/l. Comparison of the method with the Abbott TDx system showed good correlation. The Cobas-Bio method is suitable for high-risk urines since heat treatment may be performed prior to analysis.

Topics: Cocaine; Humans; Immunoassay; Substance-Related Disorders

A study was undertaken to assess the stability and the radioimmunoassay (RIA) detection of cocaine, benzoylecgonine (BZE), and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in whole blood while stored in 4 different kinds of blood collection tubes for up to 30 days at refrigeration and room temperatures. At various intervals, the tubes were sampled and analyzed using Abuscreen RIA. Also, semi-quantitative data derived from RIA analysis of forensic blood specimens were compared with quantitative data acquired using gas chromatography (GC) or GC/mass spectrometry (GC/MS) on the same specimens. RIA and chromatographic studies revealed that BZE and THC-COOH were stable in blood under all conditions studied. Cocaine, however, was found not to be stable in blood, especially when stored at room temperatures. Despite cocaine's instability in blood, RIA was able to detect the presence of cocaine and its breakdown products in blood under all conditions studied.

Topics: Blood Preservation; Chromatography, Gas; Cocaine; Dronabinol; Drug Stability; Gas Chromatography-Mass Spectrometry; Humans; Radioimmunoassay; Refrigeration; Substance-Related Disorders

Drug self-reports are often unreliable and standard blood and urine tests detect only recent cocaine use. Since cocaine is deposited in hair, we have applied a radioimmunoassay to hair extract to detect past cocaine use. Hair from 16 adult users was positive for benzoylecgonine, in the presence of negative findings from urine screening tests. Benzoylecgonine in admitted heavy users averaged 8775 ng/g of hair (range, 640 to 29,089 ng/g of hair), whereas in occasional users it averaged 624 ng/g of hair (range, 32 to 1210 ng/g of hair). Benzoylecgonine was not detected in hair of 21 adults who reported no use of cocaine ever and whose urine samples were negative for the metabolite. Neonatal hair from seven infants whose mothers were known cocaine users averaged 5430 ng of benzoylecgonine per gram of hair (range, 200 to 27500 ng/g of hair). Hair from two infants 2.5 and 3.5 months of age averaged 6050 ng of benzoylecgonine per gram of hair. However, values were negative for infants 1 year and older, corresponding to loss of fetal hair in the few months after birth. Because studies reporting reproductive risks of cocaine compare exposed and nonexposed groups, validation of drug-free status of control subjects is extremely important. Hair analysis may remedy the disadvantages of currently used methods and may identify intrauterine exposure to cocaine in babies when a maternal drug history is not available or of doubtful truthfulness.

Topics: Adult; Cocaine; Female; Hair; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications; Radioimmunoassay; Substance-Related Disorders

A rapid gas-liquid chromatographic (GLC) method was developed for the confirmation of benzoylecgonine (BE) positive urine samples screened by the enzyme multiplied immunoassay technique (EMIT) assay. The procedure is performed by solvent extraction of BE from 0.1 or 0.2 mL of urine, followed by an aqueous wash of the solvent and evaporation. The dried residue was derivatized with 50 microL of pentafluoropropionic anhydride and 25 microL of pentafluoropropropanol at 90 degrees C for 15 min. The derivatizing reagents were evaporated to dryness, and the derivatized BE, and cocaine if present, were reconstituted and injected into the gas chromatograph. The column was a 15-m by 0.2-mm fused silica capillary column, coated with 0.25 micron of DB-1, terminating in a nitrogen phosphorus detector (NPD). Cocaine and the pentafluoro BE derivatives retention times were 3.2 and 2.6 min, respectively. Nalorphine was used as reference or internal standard with a retention time of 4.78 min. The complete procedure can be performed in approximately 1.5 h. The EMIT cutoff between positive and negative urine samples is 300 ng/mL of BE. The lower limit of sensitivity of this method is 25 ng of BE extracted from urine. Validation studies resulted in confirmation of 101 out of 121 EMIT cocaine positive urine samples that could not be confirmed by thin-layer chromatography (TLC). This represents 84% confirmation efficiency.

Topics: Chromatography, Gas; Cocaine; Humans; Immunoenzyme Techniques; Substance-Related Disorders

The Keystone Diagnostic Inc (KDI) Quik Test is advertised to be an on-site, rapid, broad-spectrum paper chromatography test that is marketed for use in industry, drug abuse treatment facilities, and physician's offices. Even when unskilled individuals perform the test, five drugs of abuse, excluding marijuana, are said by the manufacturer to be reliably detected. In this study, ten confirmed drug-free urine specimens and 56 specimens positive by an immunoassay screening test, and confirmed by gas chromatography/mass spectrometry, for cocaine (n = 32), phencyclidine (n = 12), or opiate drugs (n = 12), were reanalyzed by the KDI Quik Test. The sensitivity of the KDI Quik Test was 62.5%, specificity was 70%, predictive value of a negative test was 36%, and efficiency was 64%. In too many instances the KDI Quik Test did not detect the drugs for which it is intended. Paper chromatography tests such as the KDI Quik Test are inaccurate and as such are unacceptable in any setting for the purposes of screening for drugs of abuse.

Topics: Chromatography, Paper; Cocaine; Evaluation Studies as Topic; Humans; Phencyclidine; Reagent Kits, Diagnostic; Sensitivity and Specificity; Substance-Related Disorders

Topics: Cocaine; Female; Humans; Immunoenzyme Techniques; Metabolic Clearance Rate; Social Environment; Substance Abuse Detection; Substance-Related Disorders

Topics: Adult; Cocaine; Female; Humans; Male; Middle Aged; Ophthalmic Solutions; Substance-Related Disorders

Recent studies show that the rate of cocaine use by pregnant women in the United States is much higher than realized hitherto, and an increasing number of infants are being born to cocaine-using mothers. In an ongoing research project to study the effects of cocaine on pregnancy outcome, we studied 70 infants born to cocaine-using women. These infants were matched to a drug-free comparison group selected from the population of the same hospital: children of pregnant women of a similar racial and socioeconomic distribution, but with no history or evidence of licit or illicit drug use during pregnancy. Cocaine-exposed infants had lower birth weight, shorter gestation, and a smaller head circumference than control infants. Cocaine-exposed infants also had neurobehavioral abnormalities at initial evaluation and a higher rate of perinatal complications. Toxicological evaluation of urines of neonates born to cocaine-using women showed that benzoylecgonine, a primary metabolite of cocaine, persisted in the urines for as long as 120 h after delivery. We discuss the role of the immature fetal and neonatal system in the clinical and toxicological outcome of the infant, and emphasize that further long-term studies of this will be needed.

Topics: Abnormalities, Drug-Induced; Adult; Cocaine; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Small for Gestational Age; Pregnancy; Prenatal Exposure Delayed Effects; Substance-Related Disorders; Urogenital Abnormalities

The results of 1,680 consecutive urine and serum toxicologic screens from 1,120 patients, performed in a children's hospital during a 19-month period were surveyed. Among this sample, 52 (4.6%) patients had specimens that contained cocaine and/or metabolite. Fifteen specimens contained ethanol, a benzodiazepine, or a narcotic in addition to cocaine. Four patients were neonates, whereas three were infants from 1 to 7 months of age. The remaining 45 patients were adolescents with a mean age of 19 years. Among the adolescents, 11 had a significant chronic illness. In 19 patients (37%), cocaine exposure was unsuspected until the results of testing for toxic substances were known. The reasons for hospital evaluation included depression/attempted suicide in 19 patients, seizure in five, chest pain in 5, motor vehicle accident in three, syncope in three, abdominal pain in two, pneumomediastinum in two, accidental self-immolation in one, and apnea in one. Twenty patients required medical hospitalization for a total of 268 patient-days. One patient, a neonate, died. There is a striking prevalence of cocaine exposure in the pediatric age group. Among adolescents, this exposure may occur despite the presence of chronic illness. Although the age distribution appears bimodal, infants and young children may also have unsuspected exposure to this toxin. Greater awareness of cocaine exposure in childhood will be needed by primary and tertiary care pediatricians to identify affected children and provide appropriate intervention.

Topics: Adolescent; Adult; Breast Feeding; Child; Child, Preschool; Cocaine; Cross-Sectional Studies; Female; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Male; Massachusetts; Neonatal Abstinence Syndrome; Substance-Related Disorders

This modified calibration method decreases from 300 to 27 micrograms/L the limit of detection for the cocaine metabolite (hydrolysis product), benzoylecgonine, by the Abbott Laboratories TDx fluorescence polarization immunoassay. For this determination we used 30 controls prepared from a single urine pool known to be negative for cocaine metabolite. Assay of 80 controls prepared from 20 different patients' urine samples yielded a limit of detection of 44 micrograms/L. To test these limits of detection, we analyzed 90 patients' urine samples known to be negative for cocaine metabolite and 74 patients' samples known to be positive for cocaine metabolite, using the TDx with our revised calibration. Results for two of the known negative samples and 96% of the samples containing cocaine in the 50 to 100 micrograms/L range fell above the 44 micrograms/L limit. The TDx showed excellent calibration stability. For 28 days during the test, the instrument was not recalibrated. During this period the day-to-day analysis of 50 micrograms/L controls produced a mean TDx response of 0.485 (SD 0.007) with a coefficient of variation of 1.5%.

Topics: Autoanalysis; Cocaine; False Negative Reactions; Fluorescence Polarization; Humans; Immunoassay; Mathematics; Solanine; Statistics as Topic; Substance-Related Disorders

Topics: Cocaine; Gas Chromatography-Mass Spectrometry; Hair; Humans; Substance-Related Disorders

Topics: Adult; Cocaine; Gas Chromatography-Mass Spectrometry; Humans; Male; Substance-Related Disorders; Time Factors

A retrospective study of 343 women who lacked prenatal care was conducted to ascertain the effect of recent cocaine abuse on birth weight and gestational age. All pregnant women admitted in labor to a large urban teaching hospital between January 1 and December 31, 1986 who had not received prenatal care were included. The charts of these women were evaluated to obtain information about medical and obstetric complications of pregnancy, labor and delivery, and birth weight and gestational age of the infant. Information about drug use was obtained by urine toxicology at the time of admission. Results of ordinary least-squares multiple regression analyses indicated cocaine abuse to be a significant predictor of low birth weight and early gestational age. No correlation was found between cocaine abuse and abruptio placentae or maternal hypertension.

Topics: Adolescent; Adult; Birth Weight; Cocaine; Female; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; New York City; Pregnancy; Regression Analysis; Retrospective Studies; Socioeconomic Factors; Substance-Related Disorders; Urban Population

Clinical specimens obtained from human subjects after intravenous cocaine administration were analyzed by the TDx Cocaine Metabolite Assay (TDx) and by GC/MS for benzoylecgonine. The TDx results were significantly correlated with results by GC/MS assay with no evidence of bias in the TDx assay. All cocaine metabolite positive specimens (greater than or equal to 300 ng/ml) were confirmed by GC/MS. Detection times to the last positive specimen by TDx assay and GC/MS assay of four subjects after a 20-mg intravenous dose of cocaine ranged from 29.3 to 39.1 h and 27.9 and 36.6 h, respectively. Overall, the TDx assay was found to be highly specific and accurate for the detection and measurement of benzoylecgonine in urine.

Topics: Cocaine; Gas Chromatography-Mass Spectrometry; Humans; Injections, Intravenous; Male; Substance-Related Disorders; Time Factors

A simple procedure for the determination of cocaine in human hair was described. After washing hair samples were crushed in 0.1 m HCl and incubated overnight at 45 degrees C. The acid extracts were neutralized with 1 m NaOH. Phosphate buffer (pH 7.4) was added to the extracts. The cocaine concentrations were measured by radioimmunoassay. Detection in hair was achieved in all hair samples obtained from cocaine users. This method appears to be suitable for the routine determination of cocaine.

Topics: Cocaine; Hair; Humans; Radioimmunoassay; Substance-Related Disorders

A three-year review of toxicology data from medical examiner autopsies in Pima County, Arizona, has demonstrated that cocaine has rapidly become a leading substance of abuse, second only to alcohol in the frequency of drugs detected by toxicologic analysis of all suspicious deaths, motor vehicle accident fatalities, homicides, and suicides. Gastric contents and urine were analyzed by thin-layer chromatography, and nasal swabs, blood, and urine were tested for the combination of cocaine and its metabolite benzoylecgonine by quantitative radioimmunoassay. A total of seventy-two deaths in Pima County from 1982 to 1984 have involved cocaine. Seventy percent of these have occurred in the last fifteen months. Marked variation in the individual response to cocaine compared to the blood concentration of cocaine/metabolite was noted.

Topics: Adult; Arizona; Chromatography, Thin Layer; Cocaine; Female; Gastrointestinal Contents; Humans; Male; Middle Aged; Pulmonary Edema; Radioimmunoassay; Substance-Related Disorders

Topics: Adult; Cocaine; Coronary Vessels; Female; Humans; Myocardial Infarction; Substance-Related Disorders

A thin-layer chromatography (TLC) method is described that can be used to detect benzoylecgonine (BE), a metabolite of cocaine, in human urine. It is a two-part procedure that can be integrated into a rapid screening program for drug abuse. The first part of the method utilizes two TLC solvent systems to identify a variety of drugs, including BE. The second part is specific for the cocaine metabolite and can be used as a confirmation method. The procedure is sensitive to 3-4 microgram/ml of BE in urine.

Topics: Chromatography, Thin Layer; Cocaine; Humans; Mass Screening; Microchemistry; Substance-Related Disorders