Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

This research was supported by the Medical Research Council (UK) grant MR/L010011/1 and the Intramural Research Program at the National Institute on Drug Abuse of the National Institutes of Health. Paired fetal liver and placenta samples were graciously provided by the Joint Medical Research Council/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (www.hdbr.org). The online version of this article (doi:10.1007/s11419-017-0389-2) contains supplementary material, which is available to authorized users.Peer reviewedPostprin

Development and Validation of the First Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Quantification of Multiple Antiretrovirals in Meconium

A novel method for the simultaneous quantification of 16 antiretroviral (ARV) drugs and 4 metabolites in meconium was developed and validated. Quantification of 6 nucleoside/nucleotide reverse transcriptase inhibitors, 2 non-nucleoside reverse transcriptase inhibitors, 7 protease inhibitors, and 1 integrase inhibitor was achieved in 0.25 g of meconium. Specimen preparation included methanol homogenization and solid-phase extraction. Separate positive and negative polarity multiple reaction monitoring mode injections were required to achieve sufficient sensitivity. Linearity ranged from 10 to 75 ng/g up to 2500 ng/g for most analytes and 100–500 ng/g up to 25 000 ng/g for some; all correlation coefficients were ≥0.99. Extraction efficiencies from meconium were 32.8–119.5% with analytical recovery of 80.3–108.3% and total imprecision of 2.2–11.0% for all quantitative analytes. Two analytes with analytical recovery (70.0–138.5%) falling outside the 80–120% criteria range were considered semiquantitative. Matrix effects were −98.3–47.0% and −98.0–67.2% for analytes and internal standards, respectively. Analytes were stable (>75%) at room temperature for 24 h, 4 °C for 3 days, −20 °C for 3 freeze–thaw cycles over 3 days, and on the autosampler. Method applicability was demonstrated by analyzing meconium from HIV-uninfected infants born to HIV-positive mothers on ARV therapy. This method can be used as a tool to investigate the potential effects of in utero ARV exposure on childhood health and neurodevelopmental outcomes