Determination of pethidine in human plasma by LC–MS/MS

Abstract

A sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of pethidine in human plasma was developed and validated over the concentration range of 4-2000 ng/mL. After addition of ketamine as internal standard, liquid-liquid extraction was used to produce a protein-free extract. Chromatographic separation was achieved on a 100 × 2.1 mm, 5 µm particle, Allure™ PFP propyl column, with 45:40:15 (v/v/v) acetonitrile-methanol-water containing 0.2% formic acid as mobile phase. The MS data acquisition was accomplished by multiple reactions monitoring mode with positive electrospray ionization interface. The lower limit of quantification was 4 ng/mL; for inter-day and intra-day tests, the precision (RSD) for the entire validation was less than 7%, and the accuracy was within 95.9-106.5%. The method is sensitive and simple, and was successfully applied to analysis of samples of clinical intoxication.