Detection of in utero Exposure to Cannabis in Paired Umbilical Cord Tissue and Meconium by Liquid Chromatography-Tandem Mass Spectrometry

Understanding levels of in utero drug exposure is important to properly customize the immediate, as well as ongoing, medical and social management needs of affected newborns. Here, we present the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of 4 cannabinoid analytes in two neonatal matrices. The analytes targeted were Delta(9)-tetrahydrocannabinal (THC), 11-nor-9-carboxy-THC (THCA), 11-hydroxy-THC (11-OH-THC), and cannabinol (CBN). The matrices analyzed were umbilical cord tissue and meconium. A fifth analyte, cannabidiol (CBD), was also detected uniquely in meconium. Extracts were analyzed by LC-MS/MS in negative electrospray ionization mode. Paired meconium and umbilical cord samples (i.e., one specimen from each matrix collected from each single birth, n=46 pairs) were tested to evaluate concentration and metabolite profiles. THCA was detected in all positive (containing one or more analytes) meconium samples (n=32). CBN, THC, 11-OH-THC, and CBD were present in 57% (n=26), 39% (n=18), 24% (n=11), and 20% (n=9), respectively. Concentrations were lower in the umbilical cord samples for all analytes (i.e., 0.27-537 ng/g for meconium and 0.1-9 ng/g for umbilical cord). In umbilical cord THCA was also detected in all positive samples (n=19) while THC, CBN, and 11-OH-THC were present in 24% (n=11), 17% (n=8), and 11% (n=5), respectively. Testing neonatal matrices for cannabinoids could be used to support studies designed to detect newborns exposed to cannabis in utero, as well as provide data that could be examined for correlations with clinical and social outcomes.