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一种用于测定大鼠血浆中圣草枸橼苷的高效液相色谱-串联质谱法的建立与验证及其在药代动力学研究中的应用

The development and validation of an HPLC-MS/MS method for the determination of eriocitrin in rat plasma and its application to a pharmacokinetic study.

作者信息

Li Luya, Feng Rui, Feng Xue, Chen Yuting, Liu Xin, Sun Wenjing, Zhang Lantong

机构信息

Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University Shijiazhuang 050017 P.R. China

Department of Pharmacy, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011 P.R. China.

出版信息

RSC Adv. 2020 Mar 12;10(18):10552-10558. doi: 10.1039/c9ra10925k. eCollection 2020 Mar 11.

Abstract

Eriocitrin is one of the major active constituents of lemon fruit, and it possesses strong antioxidant, lipid-lowering, anticancer and anti-inflammatory activities and has long been used in food, beverages and wine. In this study, for the first time, a rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry method (LC/MS/MS) with protein precipitation was developed and validated for the analysis of eriocitrin in rat plasma. Chromatographic separation was achieved using a mobile phase, comprising 0.1% formic acid aqueous solution and acetonitrile eluted at a flow rate of 0.8 mL min. In multiple reaction monitoring (MRM) modes, eriocitrin and internal standard (IS) were quantified using precursor-to-product ion transitions of / 595.4 → 287.1 and / 252.0 → 155.9, respectively. The intra- and inter-day precision (RSD) were below 6.79% in plasma, while accuracy (RE) was within ±7.67%. The matrix effect, recovery and stability were also demonstrated to be within acceptable limits. This method was successfully employed in the pharmacokinetic study on rats after the oral administration of eriocitrin. The pharmacokinetic parameters show that the maximum plasma concentration ( ) of eriocitrin was 299.833 ± 16.743 μg L, while the corresponding time to reach ( ) was 0.094 ± 0.019 h, and the half-time ( ) was 1.752 ± 0.323 h. The present results would be valuable for further research and development of eriocitrin.

摘要

橙皮苷是柠檬果实的主要活性成分之一,具有强大的抗氧化、降脂、抗癌和抗炎活性,长期以来一直用于食品、饮料和葡萄酒中。在本研究中,首次建立并验证了一种采用蛋白沉淀法的快速、选择性和灵敏的液相色谱-串联质谱法(LC/MS/MS),用于分析大鼠血浆中的橙皮苷。使用由0.1%甲酸水溶液和乙腈组成的流动相,以0.8 mL/min的流速进行洗脱,实现色谱分离。在多反应监测(MRM)模式下,分别使用/ 595.4 → 287.1和/ 252.0 → 155.9的前体离子到产物离子的跃迁对橙皮苷和内标(IS)进行定量。血浆中的日内和日间精密度(RSD)均低于6.79%,而准确度(RE)在±7.67%以内。基质效应、回收率和稳定性也均在可接受范围内。该方法成功应用于大鼠口服橙皮苷后的药代动力学研究。药代动力学参数表明,橙皮苷的最大血浆浓度()为299.833 ± 16.743 μg/L,而达到相应最大浓度的时间()为0.094 ± 0.019 h,半衰期()为1.752 ± 0.323 h。本研究结果将为橙皮苷的进一步研发提供有价值的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f624/9050387/309ff189fc36/c9ra10925k-f1.jpg

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