开发和验证一种灵敏和快速的UHPLC-MS/MS方法,用于在人体血中同时量化CG-0255及其活性代谢物,并将其应用于I阶段研究
Hanjing Chen1, Jiali Li1, Fei Yuan1
1Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai 200232, China.
CG-0255,一种用于急性冠状动脉综合征的新型P2Y12抗剂,可有效地转化为其活性代谢物H4.4. 一种经过验证的UHPLC-MS/MS方法可以准确量化CG-0255及其代谢物在人体血中的含量.
科学领域:
- 药理学和药物开发领域
- 分析化学 分析化学
- 临床医学 临床医学
背景情况:
- CG-0255是一种新型的硫胺P2Y12受体对抗剂.
- 它是克洛皮多格雷尔活性代谢物H4 (CG-0236) 的醇前药物.
- CG-0255正在临床开发中,用于治疗急性冠状动脉综合征.
研究的目的:
- 开发和验证一种灵敏,快速和强大的UHPLC-MS/MS方法.
- 为了使CG-0255及其衍生活性代谢物 (MP-H4,CG-0261) 在人体血中的同时量化.
- 为了支持CG-0255.5的临床开发.
主要方法:
- 开发了一种UHPLC-MS/MS方法,用于在人体血中量化CG-0255和MP-H4.
- 使用了固态提取和一个ACQUITY UPLC BEH C18柱.
- 在Q-Trap 6500+质谱仪上采用正电喷射电离和多重反应监测.
主要成果:
- 实现了总分析运行时间为7分钟,分析物和同位素的基线分离.
- 在0.05-25 ng/mL范围内的线性校准曲线证明了两种分析物.
- 在所有质量控制级别中,显示的日内和日间精度和准确度在±15%以内.
结论:
- 经过验证的UHPLC-MS/MS方法对于量化CG-0255及其在人体血中的活性代谢物具有敏感性,快速性和稳定性.
- 该方法已成功应用于I期临床研究,特征药理动力学.
- 这种可靠的测试平台支持CG-0255.5的进一步全球临床开发.
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