对伊特拉科纳和主要代谢物基伊特拉科纳用于LC-MS/MS分析的方法的验证,并应用于配方临床研究
Samuel A Krug1, Ana Luisa Coutinho1, James E Polli1
1University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD, USA.
Journal of pharmaceutical and biomedical analysis
|July 2, 2023
概括
一种新的LC-MS/MS方法有效地分析血中的伊特拉科纳 (ITZ) 和基伊特拉科纳 (ITZ-OH). 这种经过验证的试验使用最小的样本体积,并证明了对药理动力学研究的稳定性.
科学领域:
- 分析化学 分析化学
- 药理动力学 药理动力学
- 质谱测量质量谱测量
背景情况:
- 准确量化伊特拉科纳 (ITZ) 和其代谢物氧伊特拉科纳 (ITZ-OH) 对于人类的药理动力学研究至关重要.
- 新型药片配方需要强大的生物分析方法来监测药物.
研究的目的:
- 开发和验证一种高性能液体染色体协同质谱法 (LC-MS/MS) 方法,用于在人体血中量化ITZ和ITZ-OH.
- 建立一个灵敏和强大的测定方法,适合对新的ITZ配方进行临床药理动力学研究.
主要方法:
- 开发一种使用最小血体积 (100μL) 的蛋白质沉提取方法,具有优化的酸有机溶剂组成.
- 优化LC-MS/MS条件,包括监测素同位素峰值和染色学参数,以尽量减少干扰和转移.
- 对人类血中1250 ng/mL的量化范围的方法的验证.
主要成果:
- 使用简化的蛋白质沉技术,实现了与传统提取方法相似的回收.
- 通过对常见药物的干扰测试和对672个样本的成功发生样本再分析 (ISR) 来证明方法的稳定性.
- 为ITZ和ITZ-OH建立了一个经过验证的LC-MS/MS测定,具有较低的量化极限.
结论:
- 开发的LC-MS/MS方法对于分析人体血中的伊特拉科纳和基伊特拉科纳具有高效,灵敏和强大.
- 该方法的最小样本要求和已证明的可靠性使其适合对新型伊特拉科纳配方进行大规模的药理动力学研究.
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