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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

J AOAC Int. 2023 Jan 28:qsad012. doi: 10.1093/jaoacint/qsad012. Online ahead of print.

ABSTRACT

BACKGROUND: Skimmin, a potential agent for treating postpartum stroke, is one of the most important coumarins extracted from the leave of skimmia.

OBJECTIVE: In this study, a specific, sensitive and simple high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of skimmin and its metabolite umbelliferone in rat plasma was established and validated.

METHODS: 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.

RESULTS: All calibration curves shown good linearity (r > 0.995) over the concentration range of 10-10000 ng/mL 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 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 Cmax, 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.

PMID:36715062 | DOI:10.1093/jaoacint/qsad012

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