使用超和沉方法在人体血中确定未结合的度
Xia Wen1, Cathleen Doherty2, Lauren E Thompson3
1Dept of Pharmacology and Toxicology, United States of America; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ, United States of America.
Journal of pharmacological and toxicological methods
|July 2, 2024
概括
血中未结合的 (Pt) 的量化对于西斯的药理动力学至关重要. 这项研究表明,Nanosep®过器对于测量未结合的Pt是有效的,结果受到Pt水平和方法选择的影响.
科学领域:
- 药理动力学和药物新陈代谢
- 分析化学 分析化学
- 临床化学 临床化学
背景情况:
- 准确量化人体血中未结合的 (Pt) 对于了解广泛使用的化疗剂思的药理学至关重要.
- 传统的确定无结合Pt的方法,如超过和蛋白质沉,在回收和一致性方面存在局限性.
研究的目的:
- 为了比较Nanosep®过器在未结合的Pt恢复中的有效性,与传统方法 (如Centrifree®,Centrisart®,Amicon®过器和三酸 (TCA) 蛋白沉) 相比.
- 评估分子重量切线,离心力和总Pt度对人体血中未结合的Pt量化的影响.
- 为了确定在接受西斯普拉丁化疗的患者的临床样本中的未结合,结合和总Pt度.
主要方法:
- 人体血中的 (Pt) 度使用诱导合血质谱法 (ICP-MS) 来量化.
- 超过是使用Nanosep®,Centrifree®,Centrisart®和Amicon®过器进行的,这些过器具有不同的分子量切线和离心力.
- 三酸 (TCA) 蛋白沉被用作未结合的Pt确定的一种比较方法.
主要成果:
- 无结合Pt的百分比随着更高的离心速度增加,在血中增加了0.9μg/mL的Pt.
- 三酸 (TCA) 蛋白沉产生了最高的未结合Pt百分比 (42.1%) 在0.9μg/mL Pt.
- 在总Pt度≤0.9μg/mL时,未结合的Pt水平 (∼20-30%) 在测试过器中一致. 然而,超过0.9μg/mL的Pt导致与TCA沉 (63.4%79%) 相比,与超过 (36.5%48%) 相比,TCA沉的未结合分数更高.
- 在接受西斯普拉丁的患者中,未结合的Pt分数在度>0.9μg/mL时从35%到90%不等,与未结合 (R2 = 0.738) 和总Pt度 (R2 = 0.335) 相相关.
结论:
- 人体血中未结合Pt的百分比受到体外和临床样本中总和未结合Pt水平的显著影响.
- 使用Nanosep®过器进行超是一种可行且有效的方法,用于量化人体血中未结合的Pt度,为传统的蛋白质沉技术提供了可靠的替代方案.
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