Liquid chromatographic–electrospray tandem mass spectrometric determination of bisoprolol in human plasma

Abstract

An analytical method for the determination of bisoprolol in human plasma has been developed based on liquid chromatography–tandem mass spectrometry (LC–MS/MS). The analyte and internal standard (IS) diphenhydramine were cleaned up by protein precipitation with acetonitrile, reconstituted in mobile phase and separated by reversed‐phase high‐performance liquid chromatography (HPLC) using methanol:10 mm ammonium acetate:formic acid (70:30:0.1 v/v/v) as mobile phase. Detection was carried out by multiple reaction monitoring (MRM) on an LC–MS/MS system and was completed within 2.5 min. The assay was linear over the range 0.5–100 ng/mL with a limit of quantitation (LOQ) of 0.5 ng/mL. The intra‐ and inter‐day precision levels were within 5.54 and 9.95%, respectively, while the accuracy was in the range 89.4–113%. This method has been utilized in a pharmacokinetic study, where healthy volunteers were treated with an oral dose of 5 mg bisoprolol. Copyright © 2007 John Wiley & Sons, Ltd.