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超高效液相色谱-小质谱多反应监测法同时测定大鼠血浆中多种成分用于清气益气颗粒口服给药后的药代动力学研究

Simultaneous determination of multiple components in rat plasma by UHPLC-sMRM for pharmacokinetic studies after oral administration of Qingjin Yiqi Granules.

作者信息

Yang Xiaohua, Chen Shujing, Du Kunze, Shang Ye, Fang Shiming, Li Jin, Zhang Han, Chang Yanxu

机构信息

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

Front Pharmacol. 2023 Apr 13;14:1155973. doi: 10.3389/fphar.2023.1155973. eCollection 2023.

Abstract

As a Traditional Chinese Medicine prescription, Qingjin Yiqi Granules (QJYQ) provides an effective treatment for patients recovering from COVID-19. However, the pharmacokinetics characteristics of the main components of QJYQ are still unknown. An efficacious ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous determination of 33 components in rat plasma after oral administration of QJYQ. The plasma samples were precipitated with 400 µL methanol/acetonitrile (1/1, /) and analyzed in scheduled multiple reaction monitoring mode. The linear relationship of the 33 components was good (r > 0.9928). The lower limit of quantification for 33 components ranged from 0.4-60.5 ng/mL. The average recoveries and matrix effects of the analytes ranged from 72.9% to 115.0% with RSD of 1.4%-15.0%. All inter-day and intra-day RSDs were within 15.0%. After oral administration (3.15 g/kg), the validated approach was effectively applied to the pharmacokinetics of main components of QJYQ. Finally, fifteen main constituents of QJYQ with large plasma exposure were obtained, including baicalin, wogonoside, wogonin, apigenin-7--glucuronide, verbenalin, isoferulic acid, hesperidin, liquiritin, harpagide, protocatechuic acid, -Coumaric acid, ferulic acid, sinapic acid, liquiritin apioside and glycyrrhizic acid. The present research lays a foundation for clarifying the therapeutic material basis of QJYQ and provides a reference for further scientific research and clinical application of QJYQ.

摘要

作为一种中药方剂,清金益气颗粒(QJYQ)为新冠康复患者提供了有效的治疗。然而,QJYQ主要成分的药代动力学特征仍不清楚。建立并验证了一种高效超高效液相色谱-串联质谱法(UHPLC-MS/MS),用于同时测定大鼠口服QJYQ后血浆中的33种成分。血浆样品用400 μL甲醇/乙腈(1/1,v/v)沉淀,并在预定的多反应监测模式下进行分析。33种成分的线性关系良好(r>0.9928)。33种成分的定量下限为0.4 - 60.5 ng/mL。分析物的平均回收率和基质效应在72.9%至115.0%之间,相对标准偏差为1.4% - 15.0%。所有日间和日内相对标准偏差均在15.0%以内。口服给药(3.15 g/kg)后,该验证方法有效地应用于QJYQ主要成分的药代动力学研究。最后,获得了15种血浆暴露量较大的QJYQ主要成分,包括黄芩苷、汉黄芩苷、汉黄芩素、芹菜素-7-O-葡萄糖醛酸、马鞭草苷、异阿魏酸、橙皮苷、甘草苷、哈巴苷、原儿茶酸、对香豆酸、阿魏酸、芥子酸、甘草苷元芹菜糖苷和甘草酸。本研究为阐明QJYQ的治疗物质基础奠定了基础,并为QJYQ的进一步科研和临床应用提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/10133546/68d4a6447491/fphar-14-1155973-g001.jpg

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