morphine and cocaethylene

Our objective was to investigate the methodologic detection of cocaine abuse during pregnancy by determining the viability of meconium analysis for cocaine and its metabolites using chromatographic procedures as an alternative to urine testing using enzyme multiplied immunoassay technique. Our design was as follows: meconium and urine were taken from 106 very low birthweight premature babies. Meconium analysis for cocaine and its metabolites using extraction and chromatographic analysis was compared with the criterion standard immunoassay testing for urine. The work was carried out at The University of Chicago Hospital, Department of Pediatrics and the University of Illinois at Chicago, Department of Pharmacodynamics. Our patients were very low birthweight, premature babies (mean birthweight 1109 g; mean gestational age 29.1 weeks). Gender was evenly divided between male and female. The outcome measures were as follows: two active metabolites, norcocaine and cocaethylene, were detected in the meconium, but not in the urine, of some of the neonates. Determination of cocaine exposure in the newborn influenced assignment of babies in research studies as well as psychosocial evaluation and subsequent treatment of the neonate. Our results were: of the 106 meconium samples analyzed, 21 (19.8%) were positive for cocaine (n = 19, 0.24-0.78 mg/kg), norcocaine (n = 7, 0.10-0.56 mg/kg), cocaethylene (n = 1, 0.12 mg/kg) or combinations thereof. Benzoylecgonine was not detected in any of the samples. Of the urine samples analyzed by immunoassay, only 8 (7.5%) were positive for cocaine metabolites. We conclude that meconium is a better sample than urine for determining cocaine exposure in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chromatography, High Pressure Liquid; Cocaine; Dopamine Uptake Inhibitors; Female; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Infant, Premature; Male; Meconium; Pregnancy; Pregnancy Complications; Prospective Studies; Substance Abuse Detection; Urine

Cocaethylene, a metabolite of cocaine and ethanol, exhibits cardiac and neurobehavioral effects. In order to determine the prevalence of this compound in meconium specimens, samples which gave a positive result for benzoylecgonine using fluorescence polarization immunoassay were analyzed by gas chromatography/mass spectrometry for cocaine, cocaethylene and benzoylecgonine. Deuterated cocaine, cocaethylene and benzoylecgonine were used as internal standards. Gas chromatography/mass spectrometry cutoff concentrations of 5.0 ng/g were utilized for all analytes. Of the 361 specimens which consecutively confirmed positive for cocaine or benzoylecgonine, 114 (31.6%) tested positive for cocaethylene. Further, cocaethylene accumulates in greater concentrations in meconium than urine, and is a useful analyte for identifying fetal alcohol exposure.

Topics: Cocaine; Cross Reactions; Fluorescence Polarization Immunoassay; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Meconium

A selective solid-phase extraction technique has been applied to the analysis of cocaine and selected cocaine metabolites in meconium, whole blood, and plasma. This technique uses a mixed-mode Bond Elut Certify column that utilizes the characteristics of hydrophobic and polar interactions and ion exchange chromatography. Following extraction, cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene were identified and quantitated using GC/MS. Linear quantitative response curves have been generated for the metabolites over a concentration range of 0-1000 ng/g for meconium and 0-1000 ng/mL for whole blood and plasma. The overall extraction efficiencies, depending on the metabolite, were between 58.1 and 99.7% for meconium, 95.6 and 124.0% for blood, and 86.9 and 128.9% for plasma. Linear regression analyses of the standard curve for the four analytes exhibited correlation coefficients ranging from 0.850 to 0.946 for meconium, 0.939 to 0.993 for whole blood, and 0.981 to 0.996 for plasma. Because of its capability to detect cocaethylene in meconium, blood, and plasma, the procedure can be used to determine if drug exposure occurred during the latter stages of gestation and if it involved only cocaine or a combination of cocaine and ethanol.

Topics: Cocaine; Female; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Meconium; Pregnancy; Prenatal Exposure Delayed Effects; Time Factors