Rapid, simple, and economical LC-MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring

被引：13

作者：

Cheng, Yu ^{[1
,2
,3
]}

Chen, Maohua ^{[1
]}

Zhang, Bingqing ^{[2
]}

Lin, Hailin ^{[1
]}

Li, Xueyong ^{[2
]}

Cai, Yipeng ^{[1
]}

Zhang, Hui ^{[4
]}

Que, Wancai ^{[1
]}

Liu, Maobai ^{[1
]}

Qiu, Hongqiang ^{[1
,2
]}

机构：

[1] Fujian Med Univ, Dept Pharm, Union Hosp, 29 Xin Quan Rd, Fuzhou 350001, Fujian, Peoples R China

[2] Fujian Med Univ, Coll Pharm, Fuzhou, Peoples R China

[3] China Med Univ, Shengjing Hosp, Dept Pharm, Shenyang, Peoples R China

[4] Fujian Med Univ, Dept Crit Care Med, Union Hosp, Fuzhou, Peoples R China

来源：

JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS | 2022年 / 47卷 / 09期

关键词：

avibactam; ceftazidime; LC-MS; MS; simultaneous determination; therapeutic drug monitoring; RELEBACTAM; CEFEPIME; IMIPENEM;

D O I：

10.1111/jcpt.13693

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

What is Known and Objective Carbapenem-resistant Gram-negative bacterial pathogens continue to threaten public health. Avibactam (AVI), a novel non-beta-lactam beta-lactamase inhibitor, has been approved for use with ceftazidime (CAZ) mainly against carbapenem-resistant Enterobacteriaceae. Therapeutic drug monitoring (TDM) is urgently needed to optimize dosage regimens to maximize efficacy, minimize toxicity, and delay the emergence of resistance. This study aims to develop and validate a rapid, simple, and economical LC-MS/MS method for simultaneous determination of CAZ/AVI in human plasma. Methods Samples were processed by simple protein precipitation, and gradient elution strategy was applied to separate CAZ and AVI on a reverse-phase C18 column; with subsequent detection by the mass spectrometer in a positive and negative ion switching mode. Plasma samples from patients were analysed. Results and Discussion A 4-min run of LC-MS/MS was developed. The precision, trueness, matrix effect, extraction recovery, carry-over, dilution integrity, and stability were all acceptable for a bioanalytical method. The method was successfully applied to the determination of CAZ and AVI in patients, and a considerable PK variability of CAZ/AVI was observed among patients. What is New and Conclusion A robust, rapid, simple, and economical LC-MS/MS method for the simultaneous determination of CAZ and AVI was developed. The considerable PK variability of CAZ/AVI among patients demonstrates the clinical significance of TDM.

引用

页码：1426 / 1437

页数：12

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