Yang Zhi-Rui, Wang Zi-Hao, Tang Jin-Fa, Yan Yan, Yue Shi-Jun, Feng Wu-Wen, Shi Zheng-Yuan, Meng Xin-Tong, Peng Cheng, Wang Chang-Yun, Meng Da-Li, Yan Dan
Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China.
Front Pharmacol. 2018 Jun 15;9:633. doi: 10.3389/fphar.2018.00633. eCollection 2018.
Xueshuantong Lyophilized Powder (XST), consisting of a series of saponins extracted from , is widely applied to treat acute cerebral infarction, stroke, and coronary heart disease in China. However, most adverse drug reactions (ADR) in clinic are caused by quality problems of XST. In this study, six batches of certainly abnormal, four batches of possibly abnormal XST, and eight batches of normal XST were obtained from the clinical practice. Their quality fluctuations were identified by ultra-performance liquid chromatography coupled with an electrospray ionization quadrupole time-of-flight mass spectrometry operating in MS mode (UPLC-QTOF/MS) and bioassays including antithrombin and proplasmin assay. Fourteen potential components responsible for clinical ADR were identified by UPLC-QTOF/MS, especially ginsenoside Rg1, Rg3, Rb1 and notoginsenoside R1. In addition, 83.3% (5/6) and 50.0% (3/6) certainly abnormal samples could be identified by UPLC-QTOF/MS and bioassay, respectively. Interestingly, further integration of the two methods could entirely identify all the certainly abnormal samples and inferred that all the possibly abnormal samples were closely related to their quality fluctuation. It indicates that it is advisable to combine UPLC-QTOF/MS and bioassay for identifying quality fluctuation of XST, and thus reduce its ADR in clinic.
血栓通冻干粉（XST）由从[具体来源未提及]中提取的一系列皂苷组成，在中国广泛应用于治疗急性脑梗死、中风和冠心病。然而，临床上大多数药物不良反应（ADR）是由XST的质量问题引起的。在本研究中，从临床实践中获取了六批肯定异常、四批可能异常的XST以及八批正常的XST。通过超高效液相色谱-电喷雾电离四极杆飞行时间质谱联用仪（UPLC-QTOF/MS）以及包括抗凝血酶和纤溶酶原测定在内的生物测定法来识别它们的质量波动。通过UPLC-QTOF/MS鉴定出14种导致临床ADR的潜在成分，尤其是人参皂苷Rg1、Rg3、Rb1和三七皂苷R1。此外，分别通过UPLC-QTOF/MS和生物测定法可鉴定出83.3%（5/6）和50.0%（3/6）的肯定异常样本。有趣的是，将这两种方法进一步整合能够完全鉴定出所有肯定异常的样本，并推断所有可能异常的样本都与其质量波动密切相关。这表明将UPLC-QTOF/MS和生物测定法结合起来鉴定XST的质量波动是可取的，从而减少其在临床上的ADR。
