Method Development and Validation of Olprinone in Human Plasma by HPLC Coupled with ESI-MS-MS: Application to a Pharmacokinetic Study

Abstract

A simple, specific and highly sensitive assay using liquid chromatography-tandem mass spectrometry with electrospray ionization was developed for the determination of olprinone in human plasma. Following the addition of codeine as an internal standard and simple liquid-liquid extraction with ethyl acetate-isopropanol (95:5, v/v), the analytes were separated on a Zorbax SB-C18 column (4.6 × 150 mm i.d., 5 µm) and eluted with a mobile phase consisting of methanol-10 mmol/L ammonium acetate containing 1% formic acid (50:50, v/v) at a flow rate of 1.0 mL/min. Detection was achieved with electrospray positive ionization mass spectrometry using multiple reaction monitoring mode. Linear calibration curves were obtained in the concentration range of 0.1-100 ng/mL (r = 0.9995), with a lower limit of quantification of 0.1 ng/mL. The intra-day and inter-day precision values, as relative deviation, were below 6.06% and the accuracy, as relative error, was below 9.92% at all quality control concentrations. The method was applicable to clinical pharmacokinetic study of an olprinone hydrochloride hydrate injection in healthy Chinese volunteers.