Matrine determination and pharmacokinetics in human plasma using LC/MS/MS

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the determination of matrine in human plasma extracted by isopropanol:ethyl acetate (v/v, 5:95). Rapid chromatographic separation was achieved in the mobile phase composition of 5-mM aqueous ammonium acetate and acetonitrile (v/v, 70:30) with a flow rate of 0.20ml/min. Detection was carried out using positive-ion electrospray tandem mass spectrometry on a Sciex API3000. The method was accurate, specific and sensitive for the analysis of matrine in human plasma in the concentration range of 5-2000ng/ml, when huperzine A was used as internal standard. The method facilitated a clinical pharmacokinetic study after oral administration of a single dose of matrine soft gelatin capsules (100, 200 and 400mg) in a three-period crossover design. Dose-related linear trends were observed for the AUC(0-t) and the C(max) of matrine. The t(1/2) and the T(max) of matrine were independent of the administered doses.