A Rapid, Selective and Sensitive UPLC-MS/MS Method for Quantification of Nomilin in Rat Plasma and Its Application in a Pharmacokinetic Study

Abstract

Nomilin is a potential anticancer agent. In this study, a rapid, sensitive, and simple ultra-performance liquid chromatography with tandem mass spectrometry methodology was established and validated to quantify nomilin in rat plasma. Plasma samples were prepared through liquid-liquid extraction using ethyl acetate. Chromatographic separation was performed using an Acquity HSS T3 column. Acetonitrile and water containing 0.1 % (v/v) formic acid were used as mobile phases at a flow rate of 0.3 mL/min. Nomilin and quercetin (internal standard) were detected and quantified via a triple quadrupole tandem mass spectrometer in the positive ion mode with multiple reaction monitoring. Tandem mass spectrometry detection was performed by monitoring the fragmentations of m/z 515.3 → m/z 161.0 and m/z 303.2 → m/z 153.1 of nomilin and quercetin, respectively. Good linearity (R² > 0.996) was observed in the concentration range of 1 ng/mL to 500 ng/mL with a lower limit of quantification of 1 ng/mL for nomilin. The average extraction recoveries of nomilin and quercetin were > 82.3 % and 82.0 %, respectively. Intra- and interday precisions were less than 15 % and accuracy ranged from 85.0 % to 90.1 %. Indeed, the proposed method was successfully applied to analyze the pharmacokinetics of nomilin after 3 and 50 mg/kg nomilin were administered to rats via intravenous and oral routes, respectively.

Key words

Nomilin - limonoids - pharmacokinetics - UPLC-MS/MS

• References

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