Edifenphos (EDDP) [BSA]

A total of seventy samples of drinking water were tested for non-controlled and illicit drugs. Of these, 43 were from Spanish cities, 15 from seven other European countries, three from Japan and nine from seven different Latin American countries. The most frequently detected compounds were caffeine, nicotine, cotinine, cocaine and its metabolite benzoylecgonine, methadone and its metabolite EDDP. The mean concentrations of non-controlled drugs were: for caffeine 50 and 19 ng L-1, in Spanish and worldwide drinking water respectively and for nicotine 13 and 19 ng L. Illicit drugs were sparsely present and usually at ultratrace level (<1 ng L-1). For example, cocaine has mean values of 0.4 (Spain) and 0.3 ng L-1 (worldwide), whereas for benzoylecgonine, these mean values were 0.4 and 1.8 ng L-1, respectively. Higher concentrations of benzoylecgonine were found in Latin American samples (up to 15 ng L-1). No opiates were identified in any sample but the presence of methadone and EDDP was frequently detected. Total mean values for EDDP were 0.4 ng L-1 (Spain) and 0.3 ng L-1 (worldwide). Very few samples tested positive for amphetamines, in line with the reactivity of chlorine with these compounds. No cannabinoids, LSD, ketamine, fentanyl and PCP were detected. (C) 2011 Elsevier Ltd. All rights reserved.

CYP2C19 is an important member of the cytochrome P450 (CYP450) enzyme super family and is responsible for clearing approximately 10% of commonly used clinical drugs that undergo phase I metabolism. Genetic polymorphisms of CYP2C19 significantly influence the efficacy and safety of some drugs, which might cause undesirable adverse effects or cure failure at standard dosages. The aim of this study was to clarify the catalytic activities of 31 CYP2C19 alleles on the oxidative in vitro metabolism of methadone. Insect microsomes expressing the CYP2C19 alleles were incubated with 50-2000M methadone for 30min at 37 degrees C and terminated by cooling to -80 degrees C immediately. Methadone and its metabolite EDDP were analyzed by an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system. Of the 31 tested CYP2C19 allelies variants, CYP2C19*1 is the wild-type. Compared with CYP2C19*1, two CYP2C19 variants (CYP2C19*3 and *35FS) had no detectable enzyme activity, one variant L16F exhibited slightly increased intrinsic clearance values, and one variant N277K showed no significant difference. In addition, 26 variants exhibited significantly decreased values (from 1.48% to 80.40%). These findings suggest that more attention should be paid in clinical administration of methadone to individuals carrying these CYP2C19 alleles. Copyright (c) 2016 John Wiley & Sons, Ltd.