目的 建立龙胆泻肝丸中马兜铃酸I的检查方法，以了解市场上是否存在关木通替代替木通使用或者混用的问题，更好地保障本品用药安全。方法 采用Agilent SB-C18 (2.1 × 50 mm，1.8 μm) C₁₈色谱柱，以乙腈-0.1%甲酸（含5 mmol?L^-1乙酸铵）溶液为流动相梯度洗脱，流速0.3 mL?min^-1，以正离子多反应监测模式，母离子m/z 359.0，子离子m/z 298.0（定量），m/z 296.0（定性），建立了龙胆泻肝丸中马兜铃酸I的HPLC-MSn检测方法，同时对9家企业51批次龙胆泻肝丸样品进行检测。结果 51批次龙胆泻肝丸样品中有2批检出马兜铃酸I成分，涉及1家生产企业，检测结果分别为0.66 μg?g^-1、2.13 μg?g^-1；其余样品均未检出马兜铃酸I。结论 研究建立的HPLC-MS方法准确、可靠，可用于龙胆泻肝丸中马兜铃酸I的检测分析；同时，检测结果表明可能存在木通混入关木通的现象，鉴于马兜铃酸I对人体的危害性，已申请龙胆泻肝丸中马兜铃酸I检查项补充检验方法，从而为后续工作提供基础数据与科学依据，以更好地保障人民用药安全。

Objective To establish the detection method of aristolochic acid I in Longdan Xiegan Pill, and to figure out whether there are replacement of Caulis Akebiae by Caulis Aristolochiae Manshuriensis or mixed use of the 2 components in the market, to better ensure the safety of this product. Methods An Agilent SB-C18 (2.1 × 50 mm, 1.8 μm) C18 column was used with gradient acetonitrile-0.1% formic acid (containing 5 mmol?L-1 ammonium acetate) as mobile phase at a flow rate of 0.3 mL?min-1. The multi-reaction monitoring mode was used for detection with m/z 359.0 as precursor ion, product ion m/z 298.0 for quantification and m/z 298.0 for qualification. As a result, the HPLC-MS/MS method was established to detect the aristolochic acid I in all the 51 batches of samples from 9 enterprises. The HPLC-MS/MS method was further verified and used to test all samples. Results Among the 51 batches of samples, aristolochic acid I was detected in 2 batches from 1 enterprise, and the result was 0.66 μg?g-1 and 2.13 μg?g-1. Aristolochic acid I was not detected in all the other samples. Conclusion The established HPLC-MS/MS method was accurate and reliable. It could be used for detection of aristolochicacid I in Longdan Xiegan Pills. Meanwhile, there may be a mixed use phenomenon of Caulis Aristolochiae Manshuriensis and Caulis Akebiae. Due to the toxicity of aristolchic acid I, the research results have been applied as supplementary test method to provide basic data and scientific basis for the follow-up work, in order to better guarantee the drug safety.

国家自然科学基金委员会面上项目（81773874）：基于何首乌固有肝毒性假说的物质基础及肝毒性作用机制研究，负责人：马双成。