6-o-monoacetylmorphine and Drug-Overdose

A relatively overlooked aspect of forensic science is the potential of oral cavity fluid for contributing to a forensic diagnosis. Although traditional specimens, like blood and urine, are routinely evaluated for forensic toxicology testing, fluid from the oral cavity has not been investigated as a matrix in postmortem cases. Our laboratory developed and validated qualitative and quantitative analytical methods for determining 47 medicinal and illicit drugs from oral cavity fluid. These developed methods aimed to compare results from liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analyses of oral cavity fluid to those of traditional matrices collected from the same postmortem subjects. Of 34 cadavers studied, 32 (including two decomposed and two drowned subjects) had detectable and quantifiable drugs in the oral cavity fluid and/or blood, urine, bile, vitreous fluid and/or liver tissue. The most significant finding was that 6-acetylmorphine (6-AM) was detected more frequently in oral cavity fluid (11 cases) than in blood and urine combined (6 cases). Compounds with a short window of detection, like the heroin metabolite, 6-AM and even heroin, could be detected more readily in oral cavity fluid than in urine. In 2017, the incidence of heroin-related overdose deaths increased to 15,958. Those data have shed light on the practicality of testing oral cavity fluid postmortem and its significance in forensic toxicology. In conclusion, this study showed that oral cavity fluid could be useful for detecting and quantifying drugs in postmortem subjects; moreover, oral cavity fluid may be particularly suitable when other matrices are limited or difficult to collect, due to body condition or putrefaction.

Topics: Autopsy; Chromatography, Liquid; Drug Overdose; Forensic Toxicology; Heroin; Humans; Illicit Drugs; Morphine Derivatives; Mouth; Postmortem Changes; Saliva; Substance Abuse Detection; Tandem Mass Spectrometry

Brain tissue is a useful supplement to blood in postmortem investigations, but reference concentrations are scarce for many opioids. Heroin cases may be difficult to distinguish from morphine cases as heroin and its metabolites are rapidly degraded. We present concentrations from brain and blood and brain-blood ratios of 98 cases where morphine was quantified. These cases were grouped according to the cause of death: A: The compound was solely assumed to have caused a fatal intoxication. B: The compound presumably contributed to a fatal outcome in combination with other drugs, alcohol or disease. C: The compound was not regarded to be related to the cause of death. The cases were further classified as heroin cases if 6-acetyl-morphine or noscapine were detected. The analyses were carried out using solid-phase extraction or protein precipitation followed by ultra high-performance liquid chromatography coupled to mass spectrometry. The average brain-blood ratios of morphine were 1.2 and 1.8 for 69 morphine and 29 heroin cases, respectively. Differences in the brain-blood ratios were found for cases where heroin and morphine were involved in the cause of death, either in combination or on its own (P<0.001 and P=0.004, respectively). However, the overlap between morphine and heroin cases precludes the use of the brain-blood ratio to distinguish heroin from morphine intake. Morphine-6-glucuronide and 6-acetyl-morphine were quantified in brain and blood in a subset of the samples, yielding median brain-blood ratios of 5.1 and 8.3, respectively. The brain concentrations may aid the toxicological investigation in cases where heroin or morphine intoxications are suspected, but blood is not available.

Topics: Brain Chemistry; Chromatography, Liquid; Drug Overdose; Forensic Toxicology; Heroin; Humans; Mass Spectrometry; Morphine; Morphine Derivatives; Narcotics; Noscapine; Poisoning

Over the past two decades, prescription and illicit opioid use has led to changes in public health policy to address the increasing number of opioid-related deaths. The purpose of this study was to review cases from Hennepin County Medical Examiner's Office between 2004 through 2015 where heroin was listed as a significant contributor or as the cause of death. We identified 322 heroin-related deaths, which were predominantly male (255; 79%). 6-Monoacetylmorphine (6-MAM) median (range) concentrations were as follows: blood (n = 7), 0.010 (0.006-0.078) mg/L; urine (n = 30), 0.359 (0.009-1.75) mg/L; and vitreous humor (n = 31), 0.034 (0.004-0.24) mg/L. Free morphine was measurable in 273 cases and the percent free morphine (range), when grouped by COD, was opioid (n = 124), 28% (2.2%-92%), and mixed drug toxicity (n = 135), 35.3% (1.5%-100%); (p < 0.01). Quantitation of 6-MAM in blood and vitreous humor, along with a free to total morphine ratio >26%, was useful in establishing heroin-related deaths.

Topics: Accidents; Adult; Coroners and Medical Examiners; Drug Overdose; Female; Gas Chromatography-Mass Spectrometry; Heroin Dependence; Homicide; Humans; Male; Middle Aged; Minnesota; Morphine; Morphine Derivatives; Retrospective Studies; Sex Distribution; Suicide; Vitreous Body

In heroin-related deaths, it is often of interest to determine the approximate time span between intake of heroin and death, and to decide whether heroin or other opioids have been administered. In some autopsy cases, peripheral blood cannot be sampled due to decomposition, injuries or burns. The aim of the present study was to investigate whether measurements of heroin metabolites in matrices other than peripheral blood can be used to differentiate between rapid and delayed heroin deaths, and if morphine/codeine ratios measured in other matrices can separate heroin from codeine intakes.. In this study, we included 51 forensic autopsy cases where morphine was detected in peripheral blood. Samples were collected from peripheral and cardiac blood, pericardial fluid, psoas and lateral vastus muscles, vitreous humor and urine. The opioid analysis included 6-acetylmorphine (6-AM), morphine, morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G) and codeine. Urine was only used for qualitative detection of 6-AM. 45 heroin-intake cases were divided into rapid deaths (n=24), based on the detection of 6-AM in blood, or delayed deaths (n=21), where 6-AM was detected in at least one other matrix but not in blood. An additional 6 cases were classified as codeine-intake cases, based on a morphine/codeine ratio below unity (<1) in peripheral blood, without detecting 6-AM in any matrix.. The median morphine concentrations were significantly higher in the rapid compared with the delayed heroin deaths in all matrices (p=0.004 for vitreous humor and p<0.001 for the other matrices). In the rapid heroin deaths, the M3G/morphine concentration ratios were significantly lower than in the delayed deaths both in peripheral and cardiac blood (p<0.001), as well as in pericardial fluid (p<0.001) and vitreous humor (p=0.006), but not in muscle. The morphine/codeine ratios measured in cardiac blood, pericardial fluid and the two muscle samples resembled the ratios in peripheral blood, although codeine was less often detected in other matrices than peripheral blood.. Measurements of heroin-metabolites in cardiac blood, pericardial fluid and vitreous humor provide information comparable to that of peripheral blood regarding rapid and delayed heroin deaths, e.g. M3G/morphine ratios <2 indicate a rapid death while ratios >3 indicate a delayed death. However, considerable overlap in results from rapid and delayed deaths was observed, and measurements in muscle appeared less useful. Furthermore, matrices other than peripheral blood can be used to investigate morphine/codeine ratios, but vitreous humor seems less suited.

Topics: Codeine; Drug Overdose; Forensic Toxicology; Heroin; Heroin Dependence; Humans; Morphine; Morphine Derivatives; Muscle, Skeletal; Pericardial Fluid; Postmortem Changes; Time Factors; Vitreous Body

The feasibility of intervention in heroin overdose is of clinical importance. The presence of 6-monoacetyl morphine (6MAM) in the blood is suggestive of survival times of less than 20-30 minutes following heroin administration. The study aimed to determine the proportions of cases in which 6MAM was present, and compare concentrations of secondary metabolites and circumstances of death by 6MAM status.. Analysis of cases of heroin-related death presenting to the Department of Forensic Medicine Sydney, 1 January 2013-12 December 2014.. Sydney, Australia.. A total of 145 cases. The mean age was 40.5 years and 81% were male.. Concentrations of 6MAM, free morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Circumstances of death included bronchopneumonia, apparent sudden collapse, location and other central nervous system (CNS) depressants.. 6MAM was detected in 43% [confidence interval (CI) = 35-51%] of cases. The median free morphine concentration of 6MAM-positive cases was more than twice that of cases without 6MAM (0.26 versus 0.12 mg/l). 6MAM-positive cases also had lower concentrations of the other major heroin metabolites: M3G (0.05 versus 0.29 mg/l), M6G (0.02 versus 0.05 mg/l) with correspondingly lower M3G/morphine (0.54 versus 2.71) and M6G/morphine (0.05 versus 0.50) ratios. Significant independent correlates of 6MAM were a higher free morphine concentration [odds ratio (OR) = 1.7], a lower M6G/free morphine ratio (OR = 0.5) and signs of apparent collapse (OR = 6.7).. In heroin-related deaths in Sydney, Australia during 2013 and 2014, 6- monoacetyl morphine was present in the blood in less than half of cases, suggesting that a minority of cases had survival times after overdose of less than 20-30 minutes. The toxicology of heroin metabolites and the circumstances of death were consistent with 6- monoacetyl morphine as a proxy for a more rapid death.

Topics: Adolescent; Adult; Australia; Autopsy; Drug Overdose; Female; Heroin; Humans; Male; Middle Aged; Morphine; Morphine Derivatives; Narcotics; Survival Rate; Young Adult

Fentanyl induces pharmacological effects and abuse liability comparable to other prescription opioids and heroin. A surge in fentanyl-related fatalities has been periodically reported throughout the USA. The University of Florida Forensic Toxicology Laboratory observed a significant increase in fentanyl-related deaths starting in mid-2014. The present report evaluated toxicological findings, demographics of the decedents and circumstances of death in the postmortem cases that were submitted to the laboratory for toxicological analysis from July 2014 to January 2015 and that were tested for fentanyl in biological specimens. The cases originated from 6 of the 24 Florida Medical Examiner Districts, with the majority from District 12 (Desoto, Manatee and Sarasota counties). The specimens were analyzed for fentanyl by gas chromatography-mass spectrometry; the limit of detection (LOD) was 0.62 ng/mL and the limit of quantification (LOQ) was 2.5 ng/mL. During the 7-month period, the laboratory tested 143 postmortem cases for fentanyl and 50% had quantifiable fentanyl in postmortem blood. Fentanyl concentrations ranged from 2.5 to 68 ng/mL (n = 66; median: 9.8 ng/mL); six cases were positive for fentanyl >LOD but

Topics: Adult; Aged; Analgesics, Opioid; Autopsy; Benzodiazepines; Cause of Death; Cocaine; Drug Overdose; Female; Fentanyl; Florida; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Heroin; Humans; Limit of Detection; Male; Middle Aged; Morphine; Morphine Derivatives; Prevalence; Substance Abuse Detection; Young Adult

Drugs contributing to overdose deaths are listed on death certificates, but their validity is rarely studied. To assess the accuracy of "morphine" and "codeine" listings on death certificates for unintentional overdose deaths in Allegheny County, PA, investigative and laboratory reports were reviewed. Deaths were reclassified as heroin-related if documentation showed 6-monoacetylmorphine in blood or urine, "stamp bags" or drug paraphernalia at scene, history of heroin use, or track marks. Deaths were considered morphine-related if notes indicated morphine use, prescription, or morphine at scene, or codeine-related if the codeine blood level exceeded morphine. Of 112 deaths with morphine but not heroin listed on the death certificate, 74 met heroin criteria and 21 morphine criteria. Of 20 deaths with both morphine and heroin listed, only one met morphine criteria. Of 34 deaths with codeine listed, only five were attributed to codeine. Consideration of patient history, death scene evidence, and expanded toxicology testing may improve the accuracy of death certificate drug listings.

Topics: Accidents; Codeine; Coroners and Medical Examiners; Death Certificates; Drug Contamination; Drug Overdose; Forensic Toxicology; Heroin Dependence; Humans; Morphine Dependence; Morphine Derivatives; Pennsylvania

The purpose of the present study is to determine the role of lidocaine, caffeine and dextromethorphan, used as adulterant substances, in five cases of drug overdose which have come to our attention. Taking into account the pharmacological mechanism, blood concentration and route of administration (intravenous) we evaluated the hypothesis that these substances could act with a synergistic effect - or at least additive - with the illicit drugs on the central nervous system and cardiovascular system.

Topics: Adult; Anesthetics, Local; Antitussive Agents; Bile; Brain Chemistry; Caffeine; Central Nervous System Stimulants; Citalopram; Codeine; Dextromethorphan; Drug Contamination; Drug Overdose; Drug Users; Female; Forensic Pathology; Forensic Toxicology; Gastrointestinal Contents; Humans; Illicit Drugs; Kidney; Lidocaine; Liver; Lung; Male; Methadone; Morphine; Morphine Derivatives; Narcotics; Pyrrolidines; Selective Serotonin Reuptake Inhibitors; Substance-Related Disorders; Vitreous Body

The concentration of free-morphine was determined in peripheral (femoral) blood from heroin-related deaths and compared with the concentration in venous blood from impaired drivers. The presence of 6-MAM in blood or urine served as a biomarker for recent use of heroin. Males dominated over females (p<0.001) in both the autopsy cases (88%) and the drivers (91%), although their mean age was about the same 33-35 y (p>0.05). Concentrations of free-morphine in blood were not associated with age of heroin users in Sweden (p>0.05). The median concentration of free-morphine was higher in autopsy cases (0.24 mg/L, N=766) compared with apprehended drivers with 6-MAM in blood (0.15 mg/L, N=124, p<0.05), and appreciably higher than in drivers with 6-MAM in urine but not in blood (0.03 mg/L, N=1823, p<0.001). The free-morphine concentration was above 0.20mg/L in 65% of autopsy cases, 36% of drivers with 6-MAM in blood but only 1.4% of drivers with 6-MAM in urine. Poly-drug deaths had about the same concentrations of free-morphine in blood (0.24 mg/L, N=703) as heroin-only deaths (0.25 mg/L, N=63). The concentration of morphine in drug overdose deaths (median 0.25 mg/L, N=669) was about the same as in traumatic deaths among heroin users (0.23 mg/L, N=97). However, the concentration of morphine was lower when the deceased had consumed alcohol (0.18 mg/L, N=104) compared with taking a benzodiazepine (0.32 mg/L, N=94). The concentration distributions of free-morphine in blood in heroin-related deaths overlapped with the concentrations in impaired drivers, which makes the interpretation of toxicology results difficult without knowledge about tolerance to opiates in any individual case.

Topics: Adult; Automobile Driving; Benzodiazepines; Biomarkers; Central Nervous System Depressants; Codeine; Drug Overdose; Ethanol; Female; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Heroin; Humans; Male; Middle Aged; Morphine Derivatives; Narcotics; Young Adult

An accidental death caused by the combined use of a new designer drug, 4-methylmethcathinone (mephedrone), and heroin is reported. A 22-year-old Caucasian male was found unresponsive in his living quarters and was transported to the hospital where he died. During autopsy, needle marks were found along the decedent's lower legs and ankles. Investigators discovered the decedent and his roommate had been using "Black Tar" heroin and mephedrone. Routine toxicological analysis detected morphine in the decedent's blood at 0.06 mg/L. Additionally, 6-acetylmorphine, morphine, codeine, and doxylamine were detected in his urine. A designer drug screen, employing a basic liquid-liquid extraction followed by pentafluropropionic anhydride derivatization, was used to isolate mephedrone from both blood and urine specimens. The derivatized extracts were analyzed by gas chromatography- mass spectrometry (GC-MS) operating in full-scan mode. Quantitative analysis of mephedrone was performed by GC-MS operating in selective ion monitoring mode using methamphetamine-d(14) as an internal standard. Mephedrone was confirmed in the decedent's blood and urine at 0.50 and 198 mg/L, respectively. The physiological and pharmacological effects of mephedrone and any associated toxicity have not been reported. However, because of its structural similarities with methcathinone and the high concentration in the decedent's blood, the overall contribution of mephedrone to the death could not be minimized. Therefore, the medical examiner reported the cause of death as multiple-drug toxicity and the manner of death as accidental.

Topics: Amphetamine-Related Disorders; Chromatography, Gas; Codeine; Doxylamine; Drug Overdose; Fatal Outcome; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Immunoassay; Male; Methamphetamine; Morphine; Morphine Derivatives; Reproducibility of Results; Substance Abuse Detection; Young Adult

A well-established possibility to treat opiate addiction is the participation in opiate maintenance treatment programmes. For this purpose the opioids methadone and buprenorphine have been evaluated and are used nowadays in many countries. However, since 1998 also the use of slow-release oral morphine (SROM) has been legally permitted in Austria. Our data show that these morphine preparations are frequently abused and are dominating the black market in the meantime. Especially the intravenous consumption of SROM goes along with highly dangerous side effects that exceed the risks of needle sharing alone. Special galenics are supposed to ensure a 24 h effect of the otherwise quickly metabolised morphine. If dissolved and injected, insoluble contents such as talcum cause microembolisms, leading to severe damages of the inner organs. Furthermore, SROM, i.e. a drug prescribed by physicians, has been proved to be the main responsible substance in most drug related deaths since its permission and has nearly replaced heroin. Forensic physicians play a major role in the profound examination of these cases, including extensive toxicological analyses and interpretation of results. For instance, a differentiation between a recent morphine and heroin consumption is certainly possible, provided appropriate methods are used. A reliable estimation of the current situation of drug abusing habits is a premise for adequate therapeutic offers and preventive measures. Thus, well-founded and comparable data have to be collected. To facilitate data report a standardized report form has been developed that includes an obligatory statement regarding morphine or heroin consumption. This should help to enlighten the ongoing discussion on the role of SRM in drug abuse cases. Our results indicate that the prescription of SROM in opiate maintenance therapy has to be handled very strictly and should be reserved for special patients only. A slackening of the Austrian law concerning SROM is therefore objected.

Topics: Administration, Oral; Austria; Brain; Cause of Death; Delayed-Action Preparations; Drug Overdose; Foreign-Body Reaction; Heroin Dependence; Humans; Lung; Microscopy, Polarization; Morphine; Morphine Dependence; Morphine Derivatives; Myocardium; Narcotics; Pulmonary Embolism; Substance Abuse Detection; Substance Abuse, Intravenous; Talc

A liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous identification and quantification of amphetamines, diazepam and its metabolites, cocaine and its metabolites, and opiates from hair using a single extraction method. As part of the method development, Gemini C18, Synergi Hydro RP, and Zorbax Stablebond-Phenyl LC columns were tested with three different mobile phases. Analyte recovery and limit of detection were evaluated for two different solid-phase extraction methods that used Bond Elut Certify and Clean Screen cartridges. Phosphate buffer (pH 5.0) was chosen as the optimum hair incubation medium because of the high stability of cocaine and 6-monoacetylmorphine using this method and faster sample preparation. The optimized method was fully validated. Linearity was established over the concentration range 0.2-10 ng/mg hair, and the correlation coefficients were all greater than 0.99. Total extraction recoveries were greater than 76%, detection limits were between 0.02 and 0.09 ng/mg, and the intra- and interday imprecisions were generally less than 20% in spiked hair. The intra- and interbatch imprecision of the method for a pooled authentic hair sample ranged from 1.4 to 23.4% relative standard deviation (RSD) and 8.3 to 25.4% RSD, respectively, for representative analytes from the different drug groups. The percent matrix effect ranged from 63.5 to 135.6%, with most analytes demonstrating ion suppression. Sixteen postmortem samples collected from suspected drug-related deaths were analyzed for the 17 drugs of abuse and metabolites included in the method. The method was sufficiently sensitive and specific for the analysis of drugs and metabolites in postmortem hair samples. There is scope for the inclusion of other target drugs and metabolites in the method.

Topics: Amphetamines; Analgesics, Opioid; Buffers; Chromatography, High Pressure Liquid; Cocaine; Diazepam; Drug Overdose; Hair; Humans; Indicators and Reagents; Methanol; Morphine Derivatives; Phosphates; Reference Standards; Reproducibility of Results; Solid Phase Extraction; Solvents; Spectrometry, Mass, Electrospray Ionization; Substance Abuse Detection

A body packer is an important means of drug trafficking. While drug packets are inside the body, they can leak or rupture causing acute substance toxicity. Most of the reports of body packer syndrome have come from Europe and North America, which are destination targets. In the present study, the authors reported two cases of fatal heroin body packers from the northern part of Thailand. Both cases were foreign tourists who came to Chiang Mai and stayed in a hotel or a guesthouse room in which the deaths occurred. The autopsy findings revealed rupturing of heroin packages in the stomach. The packaging used in both cases was not sophisticated. The powder was packed inside condoms without extra covering, as observed in some other professional packers. The amount of heroin transported was about 30-50 gm. The purity of heroin in this powder was about 50-90%. Their destinations were their home countries and not directly to Europe or North America. Deaths occurred just prior to their return. The cause of death was a heroin overdose. A significant level of heroin metabolites, 6-MAM and morphine were detected in the blood and urine.

Topics: Adult; Condoms; Crime; Drug Overdose; Drug Packaging; Fatal Outcome; Foreign Bodies; Gastric Mucosa; Heroin; Humans; Male; Morphine Derivatives; Narcotics; Thailand; Transients and Migrants

Analyzing hair for many substances can be tedious and expensive, and a rapid screening method should prove helpful. Generally, screening has been performed using immunological tests, mainly in workplace drug testing, where the number of samples has been high. The aim of this study was to develop an LC-MS-MS method for the simultaneous analysis of several drugs of abuse in human hair as an alternative to immunological screening tests. In 75 randomly selected autopsy cases, hair was analyzed in addition to the usual specimens of blood and urine. The method included nicotine, cotinine, morphine, codeine, 6-acetylmorphine, ethylmorphine, amphetamine, methamphetamine, MDA, MDMA, benzoylecgonine, cocaine, 7-aminoflunitrazepam and diazepam. The LC-MS-MS analysis was performed on a SCIEX API 2000 MS-MS instrument equipped with an electrospray interface. To 20-50 mg of hair, 0.5 ml of mobile phase A (acetonitril:methanol:20 mM formate buffer, pH 3.0 (10:10:80)) and 25 microl of internal standard were added and the sample was incubated in a water bath at 37 degrees C during 18 h. Using a threshold of 20 ng/sample, equivalent to 1 ng/mg if 20mg hair is used, 26 positive results were found in 16 cases. Three of the 26 positive detections could not be confirmed by GC-MS. Two of the cases were not previously known as drug users. Of the 59 negative cases, only one case had a positive blood sample showing 0.01 and 0.07 microg/g femoral blood of 6-acetylmorphine and morphine, respectively. This might indicate drug abstinence resulting in decreased tolerance or even a "first time" use of heroin resulting in death. We conclude that the use of hair analysis in postmortem cases can reveal both unknown drug use, as well as confirm a period of drug abstinence prior to an acute fatal overdose. The proposed LC-MS-MS method showed high sensitivity, was very easy to perform and seemed appropriate for screening purposes.

Topics: Amphetamines; Anti-Anxiety Agents; Central Nervous System Stimulants; Chromatography, Liquid; Cocaine; Cotinine; Diazepam; Dopamine Uptake Inhibitors; Drug Overdose; Flunitrazepam; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Hair; Humans; Morphine; Morphine Derivatives; Narcotics; Nicotine; Nicotinic Agonists; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Substance Abuse Detection

Urine and blood concentrations of free and total morphin or 6-monoacetylmorphin were presented in fatal cases of morphin type opiates abuse. A solid phase extraction method was developed for isolation of drugs and their metabolities from biological material which used Separcol small columns with non-polar contents SI C 18T. Thin layer chromatography with densitometry anabled screening for quality evaluations. Resultes were compared with those obtained by fluoropolarizing immunodetection on Abbotts TDxFLx device. Possibility and cause of false positive results were discussed when using initial, screening, commercially available immunotests.

Topics: Adolescent; Adult; Chromatography, Thin Layer; Densitometry; Drug Overdose; Forensic Medicine; Humans; Male; Morphine; Morphine Dependence; Morphine Derivatives

The tissue distribution of free and conjugated morphine in a male individual who died after self-injection of heroin and methamphetamine was investigated, and the postmortem stability of morphine in the blood, liver and urine, and that of 6-monoacetylmorphine in the urine was determined. Confirmation and quantitation of morphine, 6-monoacetylmorphine and methamphetamine were performed by gas chromatography/mass spectrometry and gas chromatography, respectively. Blood levels of free and total morphine were very site-dependent with ranges of 462-1350 and 534-1570 ng/mL, respectively. Large amounts of total morphine, 5220, 4200, and 2270 ng/g, had accumulated in the stomach contents, liver, and lung, respectively. The concentration of free morphine in the cerebrospinal fluid was correlated very closely with that in the cerebrum. The proportion of free morphine in various fluids and tissues ranged from 23.0% to 98.8% of total morphine: less than 30% in the stomach contents and urine; 30-60% in the liver, cerebrospinal fluid, lung, and pericardial sac fluid; 61-90% in the spleen, right femoral muscle, myocardium, blood in the left and right ventricles of the heart, and right femoral vein blood; more than 91% in the right kidney and cerebrum. Detectable amounts of 6-monoacetylmorphine, 417 ng/mL and 78 ng/g, existed in the urine and stomach contents, respectively, indicating that this individual might have died within several hours after heroin injection. Methamphetamine concentrations in the blood were also site-dependent within the range 551-1730 ng/mL. In an in vitro experiment, free and conjugated morphine were stable in the blood and urine at 4, 18-22, and 37 degrees C for a 10-day study period. In the liver, however, conjugated morphine had been converted almost completely to free morphine at 18-22 and 37 degrees C by the end of the experiment, although it was stable at 4 degrees C. Urine 6-monoacetylmorphine, although degraded slightly at 37 degrees C, was stable at 4 and 18-22 degrees C during the experiment. Thus it appears that non-specific hydrolysis of conjugated morphine to free morphine would not occur in corpses at least for a few days after death. Femoral muscle may be a specimen of choice for roughly predicting the ratio of free to total morphine in blood even when blood specimens are not available, because the femoral muscle is relatively spared of both postmortem diffusion of drugs and bacterial invasion.

Topics: Adult; Body Fluids; Drug Overdose; Drug Stability; Gas Chromatography-Mass Spectrometry; Humans; Male; Methamphetamine; Morphine; Morphine Derivatives; Postmortem Changes; Tissue Distribution

This investigation includes whole blood samples from 53 drug addicts found unconscious in the Copenhagen area with evidence of a heroin overdose. Heroin/morphine was detected in 85% of the patients and other opioids in 11%. One or more benzodiazepines, most often diazepam, were detected in 75% of the patients. A blood alcohol concentration higher than 1.00 mg/g was detected in 57% of the patients. Methadone was detected in seven patients, ketobemidone in four, amphetamine in five and cocaine in one. This investigation showed widespread multi-drug abuse and heroin/morphine alone was detected in only one patient. As indicators of heroin intake, 6-mono-acetylmorphine (MAM) and morphine were detected in this investigation.

Topics: Adult; Denmark; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Illicit Drugs; Male; Middle Aged; Mobile Health Units; Morphine; Morphine Derivatives; Unconsciousness

We present a series of 10 fatalities involving opiate overdosage, in which morphine, codeine, and 6-monoacetylmorphine were identified and quantified, not only in postmortem biological samples, but also in pieces of underwear taken from the bodies. Small tissue samples (about 1 g) were cut off from several parts of the underwear, stored at ambient temperature until analysis, then extracted by agitation in a mixture of chloroform/2-propanol/n-heptane (60:14:26, v/v/v) and assayed using GC/MS in the single ion monitoring mode. Morphine, codeine and 6-monoacetylmorphine concentrations were in the range 0.02 to 9.27 micrograms/g. These results indicate that the impregnation of underwear by sweat and sebaceous secretions and/or urine provides detectable levels of the drugs excreted by these ways. Even in the absence of biological samples, assaying pieces of clothing may bring some evidence about the drug abuser status of their owner.

Topics: Adult; Clothing; Codeine; Drug Overdose; Female; Forensic Medicine; Humans; Male; Morphine; Morphine Derivatives; Narcotics

A procedure is presented for the simultaneous identification and quantification of morphine (MOR), codeine (COD), ethylmorphine (EM), 6-monoacetylmorphine (6-MAM), cocaine (COC), benzoylecgonine (BZE), ecgonine methylester (EME) and cocaethylene (CE), contained in the hair of opiates and cocaine addicts. The method involves decontamination in dichloromethane, pulverization in a ball mill, heat-acid hydrolysis, addition of deuterated internal standards, liquid-liquid extraction and gas chromatography/mass spectrometry (GC/MS) after silylation. The limit of detection (LOD) was approximately 0.1-0.8 ng/mg for each drug, using a 30-mg hair sample. The method is reproductible, with a coefficient of variation (CV) of approximately 8-17%. Cocaine and 6-monoacetylmorphine were the major compounds detected in cases of cocaine (14 cases) and heroin (68 cases) intake. Concentrations were in the range 0.4-78.4 ng/mg (COC), 0.0-36.3 ng/mg (BZE), 0.0-1.6 ng/mg (EME), 0.0-2.1 ng/mg (CE), 0.0-84.3 ng/mg (6-MAM), 0.2-27.1 ng/mg (MOR) and 0.1-19.6 ng/mg (COD). An application in forensic sciences, involving multi-sectional analysis, is given.

Topics: Adolescent; Adult; Calibration; Cocaine; Dopamine Uptake Inhibitors; Drug Overdose; Ethylmorphine; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Hair; Heroin; Humans; Male; Morphine; Morphine Derivatives; Narcotics; Reproducibility of Results

The concentrations of morphine and codeine were investigated in hair from the head, axillary and pubic regions obtained from 20 fatal heroin cases. Hair preparation involves decontamination procedure in dichloromethane at 37 degrees C for 15 min, solubilization in sodium hydroxide at 100 degrees C for 5 min, neutralization with hydrochloric acid and centrifugation. After extraction in chloroform/isopropanol/n-heptane (50:17:33; v/v) at pH 9.2, drugs were derivatized with BSTFA + 1% TMCS and separated on a 12-m BP-5 capillary column. Quantification was done by GC/MS using selected ion monitoring. The highest morphine concentrations were found in public hair (0.80-41.34 ng/mg), followed by hair of the head (0.62-27.10 ng/mg), and axillary hair (0.40-24.20 ng/mg). Codeine was also detected in all samples, and the codeine/morphine ratios ranged from 0.54 to 0.273. The differences observed in drug concentration in the three kinds of hair are discussed in the light of the existing literature.

Topics: Adult; Axilla; Codeine; Drug Overdose; Gas Chromatography-Mass Spectrometry; Genitalia; Hair; Head; Heroin; Humans; Illicit Drugs; Male; Morphine; Morphine Derivatives; Substance Abuse Detection

Topics: Chromatography, Gas; Drug Overdose; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Derivatives