A validated LC-MS/MS method for the determination of senkyunolide I in dog plasma and its application to a pharmacokinetic and bioavailability studies.

Senkyunolide I is one of the major bioactive components in the herbal medicine Ligusticum chuanxiong. The aim of this study was to develop and validate a fast, simple and sensitive LC-MS/MS method for the determination of senkyunolide I in dog plasma. The plasma samples were processed with acetonitrile and separated on a Waters Acquity UPLC BEH C-18 column (50 x 2.1mm, 1.7m). The mobile phase consisted of 0.1% formic acid aqueous and acetonitrile was delivered at a flow rate of 0.3mL min(-1). The detection was achieved in the positive selected reaction monitoring mode with precursor-to-product transitions at m/z 225.1 161.1 for senkyunolide I and at m/z 349.1 305.1 for an internal standard. The assay was linear over the tested concentration range, from 0.5 ng mL(-1) to 1000ng mL(-1), with a correlation coefficient >0.9992. The mean extraction recovery from dog plasma was within the range of85.78-93.25%, while the matrix effect of the analyte was within the range of98.23-108.89%. The intra- and inter-day precisions (RSD) were <12.12% and the accuracy (RR) ranged from 98.89%to 104.24%. The validated assay was successfully applied to pharmacokinetic and bioavailability studies of senkyunolide I in dogs. The results demonstrated that (a) senkyunolide I showed short elimination half-life (<1h) in dog, (b) its oral bioavailability was >40% and (c) senkyunolide I showed dose-independent pharmacokinetic profiles in dog plasma over the dose range of 1-50mg kg(-1).