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目的:建立UPLC-MS/MS法同时测定人尿液中布格呋喃2个代谢物M1和M2的浓度。方法:尿液样本用葡萄糖醛酸酶进行水解并稀释。采用Acquity BEH C_(18)(2.1 mm×50 mm,1.7μm)色谱柱,以甲醇-0.1%甲酸水溶液(75∶25)为流动相,流速0.4 m L·min~(-1),柱温35℃,进样量为10μL;采用串联四极杆质谱在ESI正离子电离模式下,应用多反应监测(MRM)扫描模式测定M1(m/z 279.1→243.1)、M2(m/z 277.2→151.2)和内标AF67(m/z 279.1→243.1)。样品分析时间为5 min。结果:M1和M2的质量浓度在10~2 000 ng·m L~(-1)范围内线性关系良好(r>0.99),批内、批间精密度和准确度以及稳定性考察项目的结果均符合要求。在单次和多次口服布格呋喃后,尿液中M1的累积排泄量分别为0.83%和1.18%,M2的累积排泄量分别为0.44%和0.72%。结论:本文建立了同时测定人尿液中布格呋喃2个代谢物(M1和M2)的UPLC-MS/MS方法,灵敏度高,特异性好,各项方法学考核的结果表明,本法可用于布格呋喃人体药代动力学的临床研究。考察了布格呋喃在中国健康人体的物料平衡和安全性等信息,结果显示尿液中M1和M2的累积排泄量很低,需要进一步研究才能获得符合要求的物料平衡数据。另外,多次口服布格呋喃后,代谢物在体内有一定量的蓄积。
OBJECTIVE: To establish a UPLC-MS / MS method for the simultaneous determination of budesonide metabolites M1 and M2 in human urine. Method: Urine samples were hydrolyzed with glucuronidase and diluted. The mobile phase was acetonitrile-0.1% formic acid (75:25) with a flow rate of 0.4 mL · min -1 on a Acquity BEH C 18 (2.1 mm × 50 mm, 1.7 μm) 35 ℃, and the injection volume was 10μL. M1 (m / z 279.1 → 243.1) and M2 (m / z 277.2 → MS) were detected by MRM in ESI positive ionization mode using tandem quadrupole mass spectrometry. 151.2) and internal standard AF67 (m / z 279.1 → 243.1). Sample analysis time is 5 min. Results: There was a good linear relationship between the concentration of M1 and M2 in the range of 10-2000 ng · m L -1 (r> 0.99). The results of the intra-and inter-batch precision and accuracy and stability study All meet the requirements. The cumulative excretion of M1 in urine was 0.83% and 1.18%, respectively, and the cumulative excretion of M2 was 0.44% and 0.72%, respectively, after single and multiple oral administration of bufogenine. Conclusion: UPLC-MS / MS method for the simultaneous determination of two metabolites of buagafuran in human urine (M1 and M2) has been established. The sensitivity and specificity are good. The results of various methodological tests show that this method can be used Pharmacokinetics of buagfuran in human. The information on the material balance and safety of buagafuran in Chinese healthy people was investigated. The results showed that the cumulative excretion of M1 and M2 in urine is very low, and further study is needed to obtain the material balance data that meets the requirements. In addition, oral administration of bufurubine several times, metabolites in the body have a certain amount of accumulation.