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UHPLC-MS/MS 法同时测定大鼠血浆中远志寡糖脂和有机酸的含量及药代动力学研究。

UHPLC-MS/MS method for simultaneous determination of Radix Polygalae glycolipids and organic acids in rat plasma and application in a pharmacokinetic study.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan 250355, China.

Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Provincial Inherit Base of Processing of Chinese Materia Medica of State Administration of Traditional Chinese Medicine, Jinan 250355, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Nov 15;1100-1101:165-173. doi: 10.1016/j.jchromb.2018.09.037. Epub 2018 Oct 2.

DOI:10.1016/j.jchromb.2018.09.037
PMID:30340065
Abstract

Radix Polygala (Yuanzhi in Chinese) is well-known in traditional Chinese medicine (TCM) and has been used for treatment of depression, brain protection, and memory improvement for thousands of years. This plant medicine is rich in saponins, glycolipids, and organic acids. The purpose of the current study was to develop a rapid, accurate, and sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of the following seven active components of Radix Polygala extracts in rat plasma: sibiricose A5 (A5); sibiricose A6 (A6); 3,6'-disinapoyl sucrose (DSS); tenuifoliside A (TFSA); tenuifoliside B (TFSB); tenuifoliside C (TFSC); and 3,4,5-trimethoxycinnamic acid (TMCA). Then, the pharmacokinetics were studied following oral administration. Plasma samples were precipitated with methanol. Chromatographic separation was successfully performed on a thermo C column (100 × 3.0 mm, 3 μm) with a mobile phase consisting of acetonitrile and 10 mmol/L of an ammonium acetate aqueous solution. Seven analytes were detected by multiple reaction monitoring (MRM) with an electrospray ionization source in the positive mode. The transitions of m/z were 517.1/174.9, 547.0/204.9, 753.2/205.2, 681.3/443.3, 667.2/205.1, 767.4/529.2, 236.8/103.2, and 136.9/92.9 for A5, A6, DSS, TFSA, TFSB, TFSC, TMCA, and salicylic acid (IS), respectively. The method validation showed good linearity in the range of 1-2000 ng/mL and LLOQs of 1 ng/mL for the 7 components in plasma. The accuracy, precision, and stability of QC samples were all within allowable ranges. In addition, no significant matrix effect was observed using this method. For the first time, the validated method has been successfully applied to the pharmacokinetic study of the seven components of Radix Polygala extracts in rat plasma. Moreover, this method may be applied for detecting prescriptions that contain Radix Polygala or other plant medicines that include one or more components above. The results of the pharmacokinetic study of the seven ingredients will provide important guidance to clinical medicine regarding Radix Polygala and prescriptions include Radix Polygala.

摘要

远志(Yuanzhi)是一种在中国传统医学(TCM)中广为人知的植物药材,已经有几千年的历史用于治疗抑郁症、保护大脑和改善记忆力。这种植物药材富含皂甙、糖脂和有机酸。本研究的目的是开发一种快速、准确、灵敏的超高效液相色谱串联质谱(UHPLC-MS/MS)法,用于同时测定大鼠血浆中远志提取物的以下七种活性成分:西伯利亚醇 A5(A5);西伯利亚醇 A6(A6);3,6'-二咖啡酰基蔗糖(DSS);远志糖苷 A(TFSA);远志糖苷 B(TFSB);远志糖苷 C(TFSC)和 3,4,5-三甲氧基肉桂酸(TMCA)。然后,进行了口服给药后的药代动力学研究。使用甲醇沉淀血浆样品。在热 C 柱(100×3.0mm,3μm)上成功进行了色谱分离,流动相由乙腈和 10mmol/L 的乙酸铵水溶液组成。通过正电喷雾源在多反应监测(MRM)模式下检测到 7 种分析物。m/z 的跃迁为 517.1/174.9、547.0/204.9、753.2/205.2、681.3/443.3、667.2/205.1、767.4/529.2、236.8/103.2 和 136.9/92.9,用于 A5、A6、DSS、TFSA、TFSB、TFSC、TMCA 和水杨酸(IS)。方法验证表明,7 种成分在血浆中的线性范围为 1-2000ng/mL,LLOQ 为 1ng/mL。QC 样品的准确度、精密度和稳定性均在允许范围内。此外,该方法观察到无显著基质效应。首次将验证方法成功应用于大鼠血浆中远志提取物七种成分的药代动力学研究。此外,该方法可能适用于检测含有远志或其他包含一种或多种上述成分的植物药材的处方。七种成分的药代动力学研究结果将为远志及包含远志的处方的临床医学提供重要指导。

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