A rapid HPLC–MS/MS method for the simultaneous determination of luteolin, resveratrol and their metabolites in rat plasma and its application to pharmacokinetic interaction studies

化学 色谱法 木犀草素 生物利用度 蛋白质沉淀 葡萄糖醛酸 电喷雾电离 甲酸 药代动力学 选择性反应监测 分析物 槲皮素 代谢物 串联质谱法 质谱法 药理学 生物化学 医学 抗氧化剂
作者
Wenying Wu,Kexin Li,Chen Zhao,Xiaohua Ran,Yu Zhang,Tianhong Zhang
出处
期刊:Journal of Chromatography B [Elsevier]
卷期号:1191: 123118-123118 被引量:18
标识
DOI:10.1016/j.jchromb.2022.123118
摘要

Both luteolin (LUT) and resveratrol (RES) are natural polyphenols that exert therapeutic effects on liver injuries. Extensive glucuronidation by uridine diphosphate-glucuronosyltransferases 1As (UGT1As) results in poor bioavailability of LUT, which limits its clinical application. As an inhibitor of UGT1A1 and UGT1A9, RES may affect the bioavailability of LUT. The purpose of this study was to develop and validate an HPLC–MS/MS method for the simultaneous determination of LUT, luteolin-3′-O-glucuronide (LUT-3′-G), RES and resveratrol-3-O-glucuronide (RES-3-G) in rat plasma to investigate the effects of RES on the bioavailability and metabolism of LUT after coadministration. The samples were extracted by protein precipitation with methanol using daidzein and naringenin as the internal standards. Separation was achieved on an XBridgeTM C18 column by isocratic elution using 88% methanol-12% water with 2 mM ammonium acetate and 0.01% formic acid. Multiple reaction monitoring mode with a negative electrospray ionization interface was used for quantification of the analytes. The calibration curves were linear over the concentration ranges of 1–1000 (r > 0.995), 2–2000 (r > 0.999), 5–5000 (r > 0.998) and 10–40000 ng/mL (r > 0.996) for LUT, LUT-3′-G, RES and RES-3-G, respectively. The method was fully validated in terms of accuracy, precision, matrix effect, recovery and stability. The validated data met the acceptance criteria in FDA guidelines. The method was successfully applied in a pharmacokinetic interaction study of LUT and RES. The results indicated that RES had a significant effect on the enhanced bioavailability of LUT by reducing the major glucuronidation metabolite in rats, which provides a reference for the combination of LUT and RES in liver diseases.
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