使用UPLC-MS/MS方法在老鼠血中同时确定iguuratimod及其代谢物:用于药物相互作用的应用
1The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Journal of pharmaceutical and biomedical analysis
|March 12, 2024
概括
这项研究开发了一种敏感的UPLC-MS/MS试验,用于在老鼠中测量iguuratimod (IGR) 和其代谢物M2. 与可纳的同时使用显著改变了IGR的药理动力学,突出了联合使用期间潜在的不良反应.
科学领域:
- 药理动力学和药物新陈代谢
- 分析化学 分析化学
- 毒理学 毒理学 毒理学
背景情况:
- 伊古拉提莫德 (IGR) 是一种需要药理动力学评估的治疗剂.
- 了解药物相互作用对于安全有效的治疗使用至关重要.
- 可纳是一种常见的抗真菌剂,可以影响药物代谢.
研究的目的:
- 建立一种灵敏的超高性能液态染色学-并联质谱法 (UPLC-MS/MS) 试验,用于量化iguuratimod (IGR) 和其代谢物M2在老鼠血中.
- 为了研究子中可纳对IGR和M2的药理动力学的影响.
主要方法:
- 开发和验证UPLC-MS/MS方法,用于同时量化IGR和M2.
- 测试使用了UPLC BEH C18柱与酸和水 (0.1%的酸) 作为移动阶段.
- 在老鼠中进行的药理动力学研究,涉及单独使用IGR与与可纳一起使用IGR的治疗.
主要成果:
- 该UPLC-MS/MS方法表现出优异的选择性,回收,准确性,精度和稳定性.
- 在老鼠中,与IGR (20 mg/kg) 及IGR (2.5 mg/kg) 同时服用可纳 (20 mg/kg) 显著增加了IGR曲线下的面积 (AUC) 和最大度 (Cmax).
- M2的药理动力学参数没有显著变化,除了终端半衰期 (t1/2z) 和最大度 (Tmax) 的时间.
结论:
- 可纳显著改变了iguuratimod在老鼠中的药理动力学.
- 这些发现表明,当iguratimod和fluconazole同时使用时,可能会增加不良反应.
- 对于管理这些药物的同时使用,需要进一步的临床关注.
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