Pharmacokinetic and excretion study of three alkaloids in rats using UPLC-MS/MS after oral administration of menispermi rhizoma capsules

Abstract

A sensitive, specific and rapid ultra-performance liquid chromatography tandem mass spectrometry method (UPLC-MS/MS) was developed for simultaneous determination of three main alkaloids (daucicoline, daurisoline, dauricine) in rat plasma, urine and feces after oral administration of menispermi rhizoma capsules. The chromatographic separation was performed on a Waters ACQUITY UPLC® BEH C₁₈ column (50 mm × 2.1 mm, id, 1.7 μm) with a column temperature of 30 °C and a linear gradient elution using a mobile phase consisting of 0.1% formic acid and acetonitrile. The flow rate was set at 0.3 mL min⁻¹, and the total run time was 10 min. The detection was performed, without interference, using positive electrospray ionization with a multiple reaction monitoring mode. A comprehensive validation of the method was performed. The linearity of the analytical response was good over a wide concentration range with correlation coefficients greater than 0.9903 and the lower limits of quantification were 1.5–5.0 ng mL⁻¹ for all matrices. Both accuracy and precision of the assay were satisfactory. The mean extraction recoveries of analytes and internal standard from rat plasma, urine and feces were all more than 78.3%. The validated methods of the three types of substrates were successfully applied to a pharmacokinetic and excretion study of the three alkaloids in rats after oral administration of menispermi rhizoma capsule. The pharmacokinetics and excretion study of these active components in menispermi rhizoma capsule have not been reported. The results provided a meaningful basis for the clinical application of menispermi rhizoma capsule.