Determination of cyclovirobuxine D in human plasma by liquid chromatography tandem mass spectrometry and application in a pharmacokinetic study

Abstract

A sensitive and reliable method based on liquid chromatography tandem mass spectrometry (LC–MS/MS) for the quantitation of cyclovirobuxine D in human plasma has been developed and validated. Sample preparation by solid phase extraction was followed by separation on a CN column with a mobile phase of methanol–water (95:5, v/v) containing 0.2% formic acid. Mass spectrometric detection in the positive ion mode was carried out by selected reaction monitoring (SRM) of the transitions at m/z 403.0→372.0 for cyclovirobuxine D and m/z 325.0→234.0 for citalopram (internal standard). The method was linear in the range 10–200 ng/L with LLOQ of 10 ng/L, recovery >85%, and no significant matrix effects. Intra- and inter-day precisions were all <9% with accuracies of 94.0–104.8%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of a 2 mg cyclovirobuxine D tablet to twenty-two healthy Chinese volunteers.

Keywords

• Cyclovirobuxine D
• LC–MS/MS
• Human plasma
• Pharmacokinetics