Quantitation of Cocaine and Metabolites, Phencyclidine, Butalbital and Phenobarbital in Meconium by Liquid Chromatography–Tandem Mass Spectrometry

Abstract

In this study, a quantitative polarity switching liquid chromatography coupled with a tandem mass spectrometer (LC-MS/MS) method was developed to detect and quantify cocaine and metabolites (cocaethylene, benzoylecgonine and meta-hydroxybenzoylecgonine), phencyclidine (PCP) and barbiturates (phenobarbital and butalbital) in meconium. Accuracy and precision samples at 0.0125% and 75% of the upper limit of quantitation (ULOQ) were analyzed in triplicate over 5 days with accuracy above 84% and average %CV values below 11%. Within-run (n = 15) and between-run (n = 15) %CV values were ≤5%. Analytical measurement ranges were reproducible and linear (R ≥ 0.995) for cocaine and metabolites (20-2,000 ng/g), PCP (10-1,000 ng/g) and barbiturates (50-5,000 ng/g). Accuracy of 100 ± 20% was observed at (the limits of detection) 10 ng/g for cocaine and metabolites, 2.5 ng/g for PCP and 25 ng/g for barbiturates. No carryover was observed at 2X ULOQ and no interfering substances were identified. Sample preparation recoveries were 53-83%. Fifty-one authentic patient samples previously characterized correlated with the newly developed test having R2 values ≥0.996. This combined method allows accurate quantitation of the targeted drugs in a complex matrix while decreasing sample preparation and analysis time with reduced sample volume. Clinical data and positivity rates were similar to previously published positivity rates. Validation data and positivity rate agreement signifies a reliable and robust assay.

Calbindin Deficits May Underlie Dissociable Effects of 5-HT6 and mGlu7 Antagonists on Glutamate and Cognition in a Dual-Hit Neurodevelopmental Model for Schizophrenia

“…Models involving social manipulations like maternal separation and isolation rearing appear to have excellent construct validity for schizophrenia, since parental separation or loss, frequent relocation during adolescence, and social disadvantage or exclusion extending into later life are all risk factors [68]. While we acknowledge that developmental exposure to glutamate receptor ligands is less common [69][70][71] it appears the long-term consequences of such exposure in rodents as part of a dual-hit approach still afford good face validity. The availability of more robust preclinical models with which to test novel therapeutics has crucial relevance for drug discovery, but to our knowledge the pharmacological sensitivity of combined versus separate PCP and isolation models has not been directly compared before.…”