[Pharmacokinetic studies of tetrahydropalmatine and dehydrocorydaline in rat after oral administration of yanhusuo extraction by LC-MS/MS method].

A sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the quantification of tetrahydropalmatine (THP) and dehydrocorydaline (DHC) in rat plasma. The compounds were simply pretreated by protein precipitation using acetone. Chromatographic separation was achieved on a reversed-phase SB-C18 column with the mobile phase of acetonitrile-ammonium acetate (0. 1% acetic acid) and step gradient elution resulted at a flow rate of 0.80 mL x min(-1). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 356. 2 --> m/z 191.9 and m/z 366. 2 --> m/z 350.2 for THP and DHC respectively. The method showed excellent linearity over the concentration range 1-1 000 ng x mL(-1) of two components (r = 0.994 for THP and r = 0.992 for DHC). The low limits of quantification were both 1 ng x mL(-1). The extract recoveries of analytes were from 71.71% to 91.59% for THP and from 83.27% to 103.15% for DHC. The precisions, the accuracy and the stability of the analytes meet the requirements. The method was applied to a pharmacokinetic study of THP and DHC after oral administration of the total alkaloid extraction of Rhizoma Corydalis (Yanhusuo). The AUC were (1.90 +/- 0.04), (2.58 +/- 0.08) and (4.34 +/- 0.19) mg x L(-1) h for low, medium and high doses of THP, respectively. While the DHC concentrations in plasma of low dose and medium dose were too lower to be detected, the AUC of high dose was (0.0896 +/- 0.0002) mg x L(-1) h.