在HSCT患者的血中同时量化tigecycline,meropenem,polymyxin B,并进行蛋白结合分析
Yan Gong1, Weijing Gong1, Junmiao Chen2
1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
一种新的UPLC-MS/MS方法准确地量化了HSCT患者的tigecycline,meropenem和polymyxin B. 抗生素与蛋白质的结合有所不同,可能受到CRE感染患者的BMI和白蛋白的影响.
科学领域:
- 药物动力学和药物监测
- 分析化学
- 血液学和干细胞移植
背景情况:
- 血造干细胞移植 (HSCT) 患者通常需要广泛的抗生素,因为感染风险很高.
- 准确量化抗生素如tigecycline,meropenem和polymyxin B对于优化免疫功能低下个体的治疗至关重要.
- 了解药物与蛋白质的结合对于解释药物动力学数据和调整剂量至关重要.
研究的目的:
- 建立和验证UPLC-MS/MS方法,用于同时量化人体血中的tigecycline,meropenem和polymyxin B.
- 在HSCT患者中确定这些抗生素的未结合分量.
- 探索影响这些抗生素在目标人群中的蛋白质结合的因素.
主要方法:
- 在人体血中开发和验证TPLC-MS/MS对tigecycline,meropenem,polymyxin B1和polymyxin B2的测定.
- 使用验证的UPLC-MS/MS方法对HSCT患者的血样本进行分析.
- 确定不同度点的蛋白质结合率 (低谷与高峰).
主要成果:
- UPLC-MS/MS方法在量化目标抗生素方面表现出高准确度,精度和稳定性.
- 观察到重要的蛋白质结合:tigecycline (82. 4%),polymyxin B1 (79. 3% - 83. 7%) 和polymyxin B2 (82. 6% - 86. 7%).
- 与高度相比,最低度的蛋白质结合通常较低.
结论:
- 经过验证的UPLC-MS/MS方法提供了一种可靠的工具,用于对HSCT患者的tigecycline,meropenem和polymyxin B的治疗药物监测.
- 在这种患者群体中,抗生素与蛋白质的结合是显著的,并且依赖于度.
- 初步发现表明,体质指数和血清白蛋白可能会影响耐卡巴胺 Enterobacteriaceae 感染的 HSCT 患者的结合,因此需要在更大的队列中进行进一步的研究.
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