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

Abstract

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 column (50 × 2.1 mm, 1.7 μm). The mobile phase consisted of 0.1% formic acid aqueous and acetonitrile was delivered at a flow rate of 0.3 mL min . 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 to 1000 ng mL , with a correlation coefficient >0.9992. The mean extraction recovery from dog plasma was within the range of 85.78-93.25%, while the matrix effect of the analyte was within the range of 98.23-108.89%. 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 (<1 h) 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 1-50 mg kg .

Research progress on the pharmacological activities of senkyunolides

“…The blocked hepatic-intestinal circulation may result in more SEI being transported from the liver into the plasma and less into the bile [15] . Moreover, SEI exhibits similar pharmacokinetic and BA profiles in rats and dogs, that is, rapid absorption, rapid clearance, moderate BA, and a dose-independent pharmacokinetic profile, suggesting that this metabolic profile may also be conserved in humans [16] .…”

Senkyunolide I: A Review of Its Phytochemistry, Pharmacology, Pharmacokinetics, and Drug-Likeness

“…The pharmacokinetic properties of SI have been studied on animals (mice, rats, and dogs) via different administration routes [35,89,90]. The results indicated that SI would be absorbed rapidly followed by short half-life (<1 h) elimination and acceptable oral bioavailability (>35%) after intragastric administration.…”