LC-MS/MS Determination and Pharmacokinetic Study of Dehydrocorydaline in Rat Plasma after Oral Administration of Dehydrocorydaline and Corydalis yanhusuo Extract

摘要

A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry method (LC-MS/MS) was developed and validated for determination of dehydrocorydaline (DHC) in rat plasma using nitidine chloride as an internal standard. The analytes were solid-phase extracted and eluted on a C18 chromatography column using a mobile phase of acetonitrile and water (containing 0.8% formic acid and 10 mM ammonium acetate) (28: 72, v/v). Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range 0.625-250 ng/mL with a quantification limit of 0.625 ng/mL. The precision was <13.7%, the accuracy >93.1%, and extraction recovery ranged from 92.1% to 107%. The validated method was successfully applied to the pharmacokinetics and excretion study of DHC in rat plasma after oral administration of pure DHC and an effective fraction of Corydalis yanhusuo (EFY). The pharmacokinetic parameters showed that DHC from EFY was absorbed more rapidly and eliminated more slowly than pure DHC. The result suggests that the differences might be due to the presence of P-glycoprotein (P-gp) inhibitors and that other alkaloids co-existing in the EFY may compete with DHC for transportation by P-gp, metabolization by P450, and binding to plasma proteins.