Detection of Cocaine, Norcocaine, and Cocaethylene in the Meconium of Premature Neonates

Abstract

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. The presence of two neuroactive metabolites, norcocaine and cocaethylene, is reported, norcocaine for the first time. Immunoassay screening procedures for urinalysis are inadequate because false-negative results are obtained.

Use of biomarkers to indicate exposure of children to organophosphate pesticides: implications for a longitudinal study of children's environmental health.

“…Only recently has the use of meconium been investigated as a potential matrix for testing of exposure to OPs. Meconium has previously been used to identify fetal exposure to illicit drugs, alcohol, and tobacco (Bearer et al 1999;Browne et al 1994;Callahan et al 1992;Clark et al 1992;Dempsey et al 1999;Maynard et al 1991;Moore et al 1998;Ostrea 1999;Ryan et al 1994) as well as the more persistent environmental toxicants, such as organochlorines and heavy metals (Hong et al 2002;Ramirez et al 2000). Meconium begins to accumulate in the bowels of human fetuses at approximately 16 weeks gestation and is generally not excreted until after delivery (Moriya et al 1994).…”

Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.

“…Prior research on a broad range of xenobiotics indicates that metabolites of compounds to which the fetus has been exposed can be detected in meconium. These include metabolites of illicit drugs (25)(26)(27)(28)(29)(30)(31)(32) , nicotine (33), alcohol (34), analgesics, antihistamines, anesthetics, the food additive butylated hydroxytoluene (BHT), and heavy metals (26). One study has also measured pesticide levels in meconium (26).…”

Meconium - biomarker in ortho- and pathomorphogenesis algorhytm. Implications in medico-legal investigation

“…By means of the chromatographic and immunochemical methods, a wide range of drugs can be determined: cocaine, amphetamines, opiates, canabinoids or phencyclidines [1,5,7,17].…”

“…Including meconium into a solvent (buffered methanol) can prevent the decrease of the drug concentration rate for 72 hours. For prolonged storing, meconium should be frozen at -15ºC [1,14,21].…”