通过UPLC-MS/MS方法在人体血中同时确定奥尔梅沙坦和甲,并将其应用于生物等价性研究
Jie Shen1,2, Lin Zhang2, Jianbang Wu2
1Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China.
一种新的超高性能液体色谱-并联质谱法 (UPLC-MS/MS) 方法准确量化了人体血中的奥尔梅沙坦和甲. 这种经过验证的方法适用于这些高血压药物的生物等价性研究.
科学领域:
- 分析化学 分析化学
- 药理动力学 药理动力学
- 生物分析是一种生物分析.
背景情况:
- 奥尔梅沙坦和酸亚胺是常见的抗高血压药物.
- 在生物矩阵中准确量化对于药理动力学和生物等价性研究至关重要.
- 现有的分析方法可能缺乏全面分析所需的灵敏度,效率或范围.
研究的目的:
- 开发和验证一种简单,灵敏和高效的超高性能液体染色学-并联质谱法 (UPLC-MS/MS) 方法.
- 为了使在人体血中同时定量确定奥尔梅沙坦和甲.
- 在生物等价性研究中应用验证的方法.
主要方法:
- 同时量化使用UPLC-MS/MS.
- 采用了稳定同位素标记的内部标准 (奥尔梅沙坦-d4和酸-13C-d2).
- 用于样品制备的蛋白质沉,ZORBAX Eclipse XDB-Phenyl柱与渐变化 (甲醇/酸),以及用于检测的多重反应监测 (MRM) 的负离子模式下的电喷射电离.
主要成果:
- 该方法在指定的范围内显示出出色的线性 (奥尔梅沙坦: 10-2000 ng/mL; 酸: 1.5-300 ng/mL).
- 对于分析品和内部标准 (87.31%-99.34%) 均实现了高平均恢复率.
- 该方法在各种等离子体条件下对选择性,准确性,精度,稳定性和矩阵效应进行了彻底验证,证实了其稳定性.
结论:
- 开发的UPLC-MS/MS方法简单,灵敏,高效,并为人类血中olmesartan和hydrochlorothiazide的同时确定得到了良好的验证.
- 该方法的可靠性和稳定性使其适合用于药理动力学和生物等价性评估.
- 在生物等价性研究中成功应用olmesartan medoxomil和hydrochlorothiazide片,证实了其在临床研究中的实用性.
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