A Sensitive LC-MS/MS Method for the Simultaneous Determination of Skimmin, a Potential Agent for Treating Postpartum Stroke, and Its Metabolite Umbelliferone in Rat Plasma

BACKGROUND: Skimmin, a potential agent for treating postpartum stroke, is one of the most important coumarins extracted from the leaves of skimmia. OBJECTIVE: In this study, a specific, sensitive, and simple high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of skimmin and its metabolite umbelliferone in rat plasma was established and validated. METHOD: Chromatographic separation was performed by an Inertsil ODS-3 column (50 mm × 4.6 mm, 5 μm) with a mobile phase consisting of 0.1% formic acid in distilled water–acetonitrile at a flow rate of 0.5 mL/min with gradient elution mode. All analytes were detected and quantified in negative multiple reaction monitoring (MRM). RESULTS: All calibration curves showed good linearity (r > 0.995) over the concentration range of 10–10 000 and 2.0–2000 ng/mL for skimmin and umbelliferone, respectively. The selectivity, sensitivity, extraction recovery, matrix effect, and stability met all requirements. CONCLUSIONS: The analysis method was successfully applied to the pharmacokinetic study of skimmin and umbelliferone in rats following oral administration of skimmin at the doses of 10, 30, and 90 mg/kg. With the exception of AUC((0-∞)) and C(max), MRT and Cl/F of skimmin had significant statistical difference with the increasing doses. Skimmin might exhibit nonlinear pharmacokinetic characteristics in rats. HIGHLIGHTS: This was the first study to investigate the pharmacokinetic characteristics of skimmin as a candidate agent for treating postpartum stroke.