morphine and 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic-acid

Cannabis misuse during pregnancy is associated with severe impacts on the mother and baby health, such as newborn low birth weight, growth restriction, pre-term birth, neurobehavioral and developmental deficits. In most of the cases, drug abuse is omitted or denied by the mothers. Thus, toxicological analyzes using maternal-fetal matrices takes place as a suitable tool to assess drug use. Herein, meconium was the chosen matrix to evaluate cannabis exposure through identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic (THCCOOH). Accelerated solvent extraction (ASE) was applied for sample preparation technique to simultaneously extract and hydrolyze conjugated THCCOOH from meconium, followed by a solid-phase extraction (SPE) procedure. The method was developed and validated for gas chromatography-mass spectrometry (GC-MS), reaching hydrolysis efficiency of 98%. Limits of detection (LOD) and quantification (LOQ) were, respectively, 5 and 10 ng/g. The range of linearity was LOQ to 500 ng/g. Inter and intra-batch coefficients of variation were <8.4% for all concentration levels. Accuracy was in 101.7-108.9% range. Recovery was on average 60.3%. Carryover effect was not observed. The procedure was applied in six meconium samples from babies whose mothers were drug users and showed satisfactory performance to confirm fetal cannabis exposure.

Topics: Dronabinol; Female; Gas Chromatography-Mass Spectrometry; Glucuronides; Humans; Hydrolysis; Infant, Newborn; Linear Models; Marijuana Abuse; Meconium; Pregnancy; Pregnancy Complications; Reproducibility of Results; Sensitivity and Specificity

Neonates that are exposed to cannabinoids in utero may have characteristic physical and mental developmental problems throughout their lives. The early identification of exposed neonates allows early intervention and anticipation of potential problems. Testing meconium detects maternal marijuana use over the last four months of gestation, providing a better drug exposure marker than urine. However, the distribution of metabolites in meconium is not identical to urine and analytical methods must be adapted. Both the major urine metabolite, 11-nor-9-carboxy-Delta9-tetrahydrocannabinol (9-carboxy-THC), and a minor urine metabolite, 11-hydroxy-Delta9-tetrahydrocannabinol (11-hydroxy-THC), are common in meconium. Currently published methods to extract these two metabolites for instrumental analysis are time-consuming and laborious, often involving the preparation of two fractions. This study describes a simple solid-phase extraction method and an optimized hydrolysis method that allow the preparation and analysis of both metabolites in a single extract. The limit of detection by this extraction method was 5 ng/g for both metabolites with an analytical measurement range from 10 to 500 ng/g. The recovery at 100 ng/g was greater than 62% for both analytes. The analysis of 246 cannabinoid screen positive specimens illustrated the importance of including the 11-hydroxy-THC in a meconium marijuana confirmation: 16 specimens confirmed positive for 11-hydroxy-THC only, resulting in a 6.5% increase in the positivity rate compared to 9-carboxy-THC alone.

Topics: Dronabinol; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Meconium; Reproducibility of Results; Sensitivity and Specificity; Substance Abuse Detection

Topics: Chromatography, High Pressure Liquid; Dronabinol; Fluorescence Polarization Immunoassay; Humans; Meconium