目的 采用UPLC-Q/TOF-MS技术对大鼠ig金振口服液后的血浆、尿液、胆汁和粪便中的原型成分及代谢产物进行分析,描绘金振口服液体内代谢轮廓,初步揭示其体内物质基础。方法 采用Waters ACQUITY^TM BEH C₁₈(100 mm×2.1 mm,1.7 μm)色谱柱,流动相为0.1%甲酸水溶液(A)-0.1%甲酸乙腈溶液(B)进行梯度洗脱,体积流量0.4 mL/min,柱温40℃。电喷雾离子源(ESI),centroid模式进行数据采集。基于高分辨质量亏损过滤技术,建立5步检识策略来表征金振口服液在大鼠体内的相关外源物。结果 大鼠ig金振口服液,在生物样本中共检识112个外源性成分,包括44个原型成分(22个成分经对照品比对)和68个代谢产物,主要的代谢途径为II相代谢葡萄糖醛酸化、硫酸化及I相代谢甲基化等。结论 采用UPLC-Q/TOF-MS技术及建立的检识策略可对金振口服液在大鼠血浆、尿液、粪便和胆汁中的外源物进行快速有效的定性检识,有助于揭示其体内药效成分,为其药动学特征的描绘及建立与功效相关联的质量控制方法提供一定的参考依据。

Objective To study the prototypes and their metabolites in rat plasma, urine, bile and feces after intragastric administration of Jinzhen Oral Liquid (金振口服液, JZOL) by UPLC-Q/TOF-MS technique. Methods A Waters ACQUITY^TM BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) was used for gradient elution with mobile phase 0.1% formic acid aqueous solution (A) and 0.1% formic acid acetonitrile (B), and the flow rate was 0.4 mL/min, the column temperature was 40℃. Electrospray ion (ESI) source was applied for the qualitative analysis under the positive and negative ion modes. Data is collected in centroid mode. Mass defect filter (MDF) technique and a five-step strategy were established to characterize the related xenobiotics of JZOL in four biological samples of rats. Results A total of 112 xenobiotics were identified, including 44 prototype components and 68 metabolites, of which 22 prototype components were identified with reference substance. The main metabolic pathways were phase Ⅱ metabolic reactions (mainly including glucuronidation and sulfonation) and phase Ⅰ metabolic methylation, etc. Conclusion The established five-step strategy based on UPLC-Q/TOF-MS technique can be used for the rapid and effective qualitative identification of the xenobiotics in rat plasma, urine, feces and bile after oral administration of JZOL, which would be helpful to reveal the effective components in vivo. It provides some reference for the characterization of pharmacokinetic characteristics and the establishment of quality control methods related to efficacy.

R284.1

江苏省省级工业和信息产业转型升级专项资金项目：多组分中药研究关键技术；国家自然科学青年基金资助项目（81903426）