Determination of avibactam and ceftazidime in human plasma samples by LC-MS
Determination of avibactam and ceftazidime in human plasma samples by LC-MS
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DOI：
10.4155/bio.15.76
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发表时间：
2015-01-01
期刊：
影响因子：
1.8
通讯作者：
Glendining, Karen
中科院分区：
文献类型：
--
作者：
Sillen, Henrik;Mitchell, Richard;Glendining, Karen
目的：阿维巴坦是一种新型的非-内酰胺类-内酰胺酶抑制剂，与-内酰胺类抗生素头孢他啶合用，正在临床开发中。评价其PK和PD的需要需要准确可靠的生物分析方法。方法：我们描述了测定人血浆中阿维巴坦和头孢他啶的LC-MS/MS方法。使用弱阴离子交换固相萃取法提取阿维巴坦，并在酰胺柱上进行分析。头孢他啶用蛋白沉淀法提取，C18柱分析。在10 - 10，000 ng/ml（阿维巴坦）和43.8 - 87，000 ng/ml（头孢他啶）范围内建立校准曲线。结果与结论：方法验证、三个实验室间的交叉验证和真实样品的再分析证明了方法的稳健性。该方法已成功应用于多项临床研究。
Aim: Avibactam, a novel non--lactam -lactamase inhibitor co-administrated with the -lactam antibiotic ceftazidime, is in clinical development. The need to evaluate its PK and PD requires accurate and reliable bioanalytical methods. Methods: We describe LC-MS/MS methods for the determination of avibactam and ceftazidime in human plasma. Avibactam was extracted using weak anionic exchange solid-phase extraction and analyzed on an amide column. Ceftazidime was extracted using protein precipitation and analyzed on a C18 column. Calibration curves were established over 10-10,000 ng/ml (avibactam) and 43.8-87,000 ng/ml (ceftazidime). Results & conclusion: Method validation, cross-validation between three laboratories and incurred sample re-analysis demonstrated method robustness. The methods were successfully applied to multiple clinical studies.