通过超过确定抗生素的自由血清度:对实验变量的广泛评估
Constantin Lier1, Alexander Dejaco2, Alexander Kratzer3
1Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
Bioanalysis
|July 23, 2024
概括
实验条件显著影响无抗生素血清度. 保持生理pH值至关重要,比严格的体温控制更重要,用于准确的未结合分数测量.
科学领域:
- 药理动力学和药物新陈代谢
- 分析化学 分析化学
- 生物化学 生物化学
背景情况:
- 准确确定自由血清药物度对于治疗药物监测和了解药物疗效至关重要.
- 与HPLC-DAD相结合的超过是评估未结合药物分量的常见方法.
- 实验条件的变化可以影响蛋白质结合,从而影响未结合的分数 (f_u).
研究的目的:
- 评估不同的实验条件如何影响各种抗生素的测量自由血清度.
- 将在不同条件下获得的结果与超过分析的标准方案进行比较.
主要方法:
- 无抗生素血清度通过超过和高性能液体染色学与二极管阵列检测 (HPLC-DAD) 来确定.
- 关键的实验参数包括相对离心力 (RCF),温度,pH和缓冲器类型被系统地改变.
- 结果与标准协议 (酸盐缓冲区,pH 7.4,37°C,1000 x g) 相比进行了基准测试.
主要成果:
- 不结合的分量 (f_u) 通常随着分子量增加而减少,在22°C下降,而不是37°C.
- 没有缓冲的血清增加了克洛西林和瓦尔酸的含量,同时显著降低了基本或两药物的含量.
- 酸盐和HEPES缓冲剂产生了相似的结果,除了易形成金属酸盐复合物的药物.
结论:
- 维持生理pH值是一个比严格遵守体温更关键的因素,以准确地确定未结合的分数.
- 优化的实验条件对于可靠地评估血清中的抗生素药理动力学是必不可少的.
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