目的 基于中药传统用法的科学解析，以吴茱萸为例，建立中药毒性质量标志物（Q-Marker）的辨识技术。方法 以吴茱萸水煎时“久煎”和“汤洗”的传统用法的文献研究为切入点，运用指纹图谱和质谱技术对吴茱萸水煎液的成分进行表征，以正常人肝细胞（L02）的生长抑制率、乳酸脱氢酶（LDH）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）等指标对吴茱萸水煎液的体外肝毒性进行评价，采用灰色关联分析法进行“谱-毒”相关分析。结果 吴茱萸水煎液的肝毒性随着煎煮时间的延长，存在先升高后降低的变化趋势，通过“谱-毒”关联分析发现，大极性成分可能是吴茱萸水煎液中的肝毒性Q-Marker，通过液质联用解析为咖啡酰葡萄糖酸异构体，揭示了吴茱萸“久煎”和“汤洗”的科学内涵，建立了基于吴茱萸传统用法的肝毒性Q-Marker辨识技术。结论 中药传统用法的科学解析作为中药毒性Q-Marker辨识的切入点具有可行性。

Objective To establish a method for the toxic Q-Marker identification of traditional Chinese medicine (TCM), based on the scientific analysis on the conventional application of TCM and taking Euodiae Fructus as a case study. Methods Taking the literature research of the conventional application of "Jiu Jian" and "Tang Xi" as the breakthrough point, the components of Euodiae Fructus decoction were characterized by fingerprint and mass spectrometry technology, and the hepatotoxicity of Euodiae Fructus decoction was evaluated by the growth inhibition rate, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) of normal human liver cells (L02). The "spectrum-toxicity" relationship analysis was performed by grey relational analysis. Results The hepatotoxicity of Euodiae Fructus decoction first increased and then decreased with the prolongation of boiling time. Through the "spectrum-toxicity" relationship analysis, it was found that the polar components could be the hepatotoxic Q-Marker in Euodiae Fructus decoction, and the polar components were characterized as isomers of caffeoyl gluconic acid. The scientific connotation of "Jiu Jian" and "Tang Xi" was revealed and the hepatotoxic Q-Marker identification method of Euodiae Fructus was established. Conclusion It is feasible to take the scientific analysis of conventional application as the breakthrough point for the toxic Q-Marker identification of TCM.

国家重点基础研究发展计划（“973”）中医基础理论专项资助项目课题2（2009CB522802）；国家重大新药创制重大专项课题：中药复方药理学研究与药效评价关键技术（2009ZX09502-015）；山东省自主创新和成果转化课题：药物安全性评价和适宜于抗肿瘤及缺血性脑血管疾病多靶点和复方新药成药性评价关键技术研究（2014ZZCX02104）；山东省中医药科技发展计划课题：吴茱萸肝毒性氧化损伤路径与凋亡机制研究（2013-120）；泰山学者工程专项经费资助（Ns201511107）