Servais Anne-Catherine, Janicot Bertrand, Takam Arnold, Crommen Jacques, Fillet Marianne
Laboratory for the Analysis of Medicines, Dept. of Pharmacy, CIRM, University of Liège, CHU, B36, B-4000 Liege, Belgium.
Laboratory for the Analysis of Medicines, Dept. of Pharmacy, CIRM, University of Liège, CHU, B36, B-4000 Liege, Belgium.
J Chromatogr A. 2016 Oct 7;1467:306-311. doi: 10.1016/j.chroma.2016.07.022. Epub 2016 Jul 9.
A LC method using a chiral stationary phase (CSP) with cellulose tris(3-chloro-4-methylphenylcarbamate) as chiral selector in polar organic mode (POM) was developed for the separation of the biopharmaceutic classification system (BCS) class II chiral prodrug eslicarbazepine acetate (ESL) and its main metabolites, namely eslicarbazepine, its optical antipode, (R)-licarbazepine, and the achiral oxcarbazepine (OXC). The percentage of methanol (MeOH) in the mobile phase containing acetonitrile (ACN) as the main solvent was found to significantly influence analyte retention and resolution. A reversal of elution order of OXC and (R)-licarbazepine was observed, depending on the MeOH percentage in the mobile phase. The optimized mobile phase consisted of ACN/MeOH/acetic acid/diethylamine (95/5/0.2/0.07; v/v/v/v). The potential of this chemo- and enantioselective LC method combined with solid-phase extraction (SPE) was then evaluated for in vitro metabolism studies using ESL as a model case. Only eslicarbazepine could be detected after incubation of ESL in human liver microsome systems.
开发了一种液相色谱（LC）方法，该方法采用手性固定相（CSP），以三（3-氯-4-甲基苯基氨基甲酸酯）纤维素作为手性选择剂，在极性有机模式（POM）下用于分离生物药剂学分类系统（BCS）II类手性前药醋酸艾司卡比平（ESL）及其主要代谢物，即艾司卡比平、其旋光对映体（R）-卡马西平以及非手性的奥卡西平（OXC）。发现以乙腈（ACN）作为主要溶剂的流动相中甲醇（MeOH）的百分比对分析物保留和分离度有显著影响。根据流动相中MeOH的百分比，观察到OXC和（R）-卡马西平的洗脱顺序发生了反转。优化后的流动相由ACN/MeOH/乙酸/二乙胺（95/5/0.2/0.07；v/v/v/v）组成。然后以ESL为模型案例，评估了这种化学和对映体选择性LC方法与固相萃取（SPE）相结合用于体外代谢研究的潜力。在人肝微粒体系统中孵育ESL后，仅能检测到艾司卡比平。
