Development and validation of a sensitive U-HPLC–MS/MS method with electrospray ionization for quantitation of ranolazine in human plasma: Application to a clinical pharmacokinetic study

Abstract

A simple, sensitive and high-throughput ultra high-performance liquid chromatography electrospray ionization mass spectrometry (U-HPLC–ESI-MS/MS) method has been developed and validated for the determination of ranolazine in human plasma. Propafenone was employed as the internal standard (I.S.). The analytes were chromatographically separated on a BEH C18 column (50mm×2.1mm, 1.7μm) with a mobile phase consisting of acetonitrile and aqueous ammonium acetate solution (0.06% formic acid, 7.5mmolL−1 ammonium acetate, 40:60, v/v). Detection of the analytes was achieved using positive ion electrospray ionization via multiple reactions monitoring mode. The mass transitions were m/z 428.3→279.3 for ranolazine and m/z 342.4→115.9 for propafenone. The assay was linear over the concentration range 1–3000ngmL−1, with correlation coefficients ≥0.997. The intra- and inter-day coefficients of variation were less than 8.9% in terms of relative standard deviation and accuracy ranged from 93.0 to 108.9% at all quality control levels. The validated method was a simple sample preparation procedure and short run-time (<2.0min) method, which was successfully applied to a phase I pharmacokinetic study of ranolazine in Chinese healthy volunteers.