Detection of in utero cannabis exposure by umbilical cord analysis

Abstract

According to the 2014 National Survey on Drug Use and Health, 5.3% of pregnant women smoked marijuana in the past month. This prevalence is expected to increase as a growing number of states and countries are now considering legalization. Although the umbilical cord is becoming a useful objective tool to detect in utero drug exposure, currently data about analytical methods and its utility to detect cannabis exposure are scarce. The objective of this work was to develop a method for the determination of Δ -tetrahydrocannabinol (THC), 11-hydroxyTHC (THC-OH), 11-nor-9-carboxy-THC (THCCOOH), 8-β-11-dihydroxyTHC (THC-diOH), THC and THCCOOH glucuronides, and cannabidiol (CBD) in the umbilical cord by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dual ionization source. Umbilical cord samples (0.5 g) were homogenized in methanol and extracted by solid-phase extraction. Reversed-phase chromatographic separation was performed in 14 minutes, and 2 transitions per analyte were monitored in multiple reaction monitoring mode. Method validation included linearity (1-10 to 20-200 ng/g), precision (4.1%-23.4%), accuracy (87.5%-111.4%), matrix effect (-54.8% to -5.8%), extraction efficiency (25%-45.6%), limits of detection and quantification (1-10 ng/g), and endogenous (n = 5) or exogenous interferences (not detected). The method was applied to 13 authentic samples from cannabis-exposed newborns, which meconium samples had tested positive for cannabis. Twelve cord specimens tested positive for THCCOOH-glucuronide (1.6-19.1 ng/g). We developed and validated a specific and sensitive method for the simultaneous determination of THC, its metabolites, including THC and THCCOOH glucuronides, and CBD in umbilical cord samples by LC-MS/MS. The analysis of authentic samples showed the usefulness of umbilical cord to detect cannabis in utero exposure.

Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination

“…Regarding maternal and neonatal biological specimens, the identification and quantification of drugs and their metabolites offer an objective and reliable approach. Among these specimens, meconium has been widely employed to identify foetal drug exposure during the 3rd trimester [275,296,297]. The main metabolite of THC, THC–COOH, has been reported as the most abundant metabolite detected in meconium samples [298].…”

“…This specimen is available immediately at birth, for all neonates, and a large amount of tissue is usually available for the analysis [299]. The cannabis data in this sample is scarce and not much information is available on metabolite profile [297].…”

Screening Pregnant Women and Their Neonates for Illicit Drug Use: Consideration of the Integrated Technical, Medical, Ethical, Legal, and Social Issues

“…Absolute quantitation could not be determined due to cross reactivity in excess of 100% for certain opioid metabolites, but the method showed perfect selectivity for cords in the study that were deemed opioid positive by clinical diagnostics. Most recently, the umbilical cord has been shown to be a sensitive and specific screening tissue for cannabis use (Kim et al, 2018). The authors showed excellent concordance with meconium, and were able to absolutely quantitate tetrahydrocannabinol (THC) as well as several of its hydroxyl and glucuronide metabolites.…”

Cannabis “in utero”: the fetus as a compulsive consumer

“…Cannabis is the generic term used to denote plant-derived psychoactive substances prepared from C. sativa, and consists of approximately 60 plant-derivative cannabionid compounds denominated phytocannabinoids. In addition to these, there are two other types: the endocannabinoids (naturally produced by the body) and the synthetic cannabinoids (eliciting cannabis effects, generally with a higher potency than endocannabinoids) [16]. The most important psychoactive phytocannabinoid is the delta-9-tetrahydrocannabinol (delta9THC), a partial agonist of the endocannabinoids receptors CBr1 and CBr2, the ativation of which generates central and peripheral effects [17][18][19][20][21].…”