Determination of vinpocetine and its primary metabolite, apovincaminic acid, in rat plasma by liquid chromatography–tandem mass spectrometry

Abstract: A precise and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous determination of vinpocetine (VP) and its primary metabolite, apovincaminic acid (AVA), in rat plasma was developed and validated. The analytes and the internal standard-dimenhydrinate were extracted from 50μL aliquots of rat plasma via solid–liquid extraction. Chromatographic separation was achieved in a run time of 3.5min on a C18 column under isocratic conditions. Detection of analytes and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for VP, AVA and IS were m/z 351.4→280.2, 323.2→280.2 and 256.2→167.3 respectively. The method was fully validated for its sensitivity, selectivity, accuracy and precision, matrix effect, stability study and dilution integrity. A linear dynamic range of 0.5–500ng/mL for both VP and AVA was evaluated with mean correlation coefficient (r) of 0.9970 and 0.9984 respectively. The precision of the assay (RSD%) was less than 8.55% at all concentrations levels for both VP and AVA. This method was successfully applied to a pharmacokinetic study of VP in rats after intravenous (1mg/kg) and oral (1mg/kg) administration. [Copyright &y& Elsevier]