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

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. [ABSTRACT FROM AUTHOR]