Simultaneous determination of six alkaloids and one monoterpene in rat plasma by liquid chromatography–tandem mass spectrometry and pharmacokinetic study after oral administration of a Chinese medicine Wuji Pill

A simple and sensitive method for simultaneous determination of seven active constituents, jatrorrhizine, berberine, coptisine, palmatine, evodiamine, rutacarpine and paeoniflorin, from a Chinese medicine Wuji Pill in rat plasma was developed based on a liquid chromatography and tandem mass spectrometry method. The separation of these seven compounds was carried out on a Shiseido CAPCELL PAK C18 column using a mobile phase consisting of acetonitrile (containing 0.1% formic acid and water (containing 0.1% formic acid and 10 mmol/L ammonium acetate) and carbamazepine as an internal standard. Electrospray ionization in positive-ion mode and multiple reaction monitoring was used to identify and quantitate active components. All calibration curves gave good linearity (r > 0.993) over the concentration range from 0.42–208.0 ng/mL to 4.18–418.0 ng/mL for all components. The precision of the in vivo study was evaluated by intra- and inter-day assays and the percentages of relative standard deviation were all within 15%. The method was successfully applied to pharmacokinetic study of all six alkaloids and one monoterpene in rat plasma after oral administration of the Wuji Pill.

► LC–MS/MS method for simultaneous quantitation of six alkaloids and one monterpene. ► Seven active constituents of “Wuji Pill” simultaneously quantitated in rat plasma. ► LLOQs of these seven constituents are below 4.18 ng/mL. ► Efficient one-step liquid–liquid extraction of these constituents in rat plasma. ► Pharmacokinetic of seven compounds in rat plasma after oral dosing of “Wuji Pill”.