人体血中Evocalcet的定量LC-MS/MS试验:在健康的中国志愿者中进行禁食和食的比较药理动力学评估
Keran Chen1, Orwa Siddig2, Jucui Yang1
1Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, China.
概括
一种新的LC-MS/MS方法准确地量化了血中的埃沃卡塞特. 这就是Evocalcetcet.
科学领域:
- 药理动力学和药物新陈代谢
- 分析化学 分析化学
- 生物分析是一种生物分析.
背景情况:
- 埃沃卡塞特是一种新型治疗剂,需要强大的生物分析方法进行临床研究.
- 了解evocalcet的药理动力学特征对于优化其治疗用途至关重要.
- 现有的分析方法可能缺乏在生物矩阵中准确量化所需的灵敏度或特异性.
研究的目的:
- 开发和验证一种灵敏可靠的液体染色学-并联质谱法 (LC-MS/MS) 方法,用于量化人类血中的埃沃.
- 在被食和禁食条件下,在健康志愿者中描述埃沃的药理学特征.
- 为了比较evocalcet在健康个体与甲状腺功能过高患者中的药理动力学.
主要方法:
- 使用LC-MS/MS与evocalcet-d4作为内部标准对人体血中的evocalcet进行定量分析.
- 根据国际协调理事会 (ICH) 的指导方针验证方法,评估线性,准确性,精度和量化极限.
- 在口服使用evocalcet后,在健康的中国志愿者 (禁食或食后) 和甲状腺功能障碍患者的药理动力学研究.
主要成果:
- 经过验证的LC-MS/MS方法显示出极好的线性 (R2>0.99) 和1 ng/mL的低量化极限 (LLOQ).
- 与食后条件相比,禁食条件下埃沃卡塞特暴露 (Cmax和AUC) 显著更高,Tmax延迟.
- 高甲状腺患者的药用动力学参数 (Cmax,Tmax,t1/2,AUC) 与健康个体相比,表明吸收和处置发生变化.
结论:
- 一种强大且经过验证的LC-MS/MS方法可以准确量化人类血中的埃沃.
- 食物摄入显著影响evocalcet的口服生物可用性和药理动力学特征.
- 该研究提供了必要的药理动力学数据和方法见解,以促进evocalcet的临床开发,并了解其安全性和有效性.
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