中国药物警戒 ›› 2025, Vol. 22 ›› Issue (10): 1109-1113.
DOI: 10.19803/j.1672-8629.20240847

• 基础与临床研究 • 上一篇    下一篇

人血浆中头孢他啶和阿维巴坦浓度测定的液相色谱串联质谱法建立

刘彤彤1,3, 郭星辰1,3, 张冬婕1,3, 陈启2, 赵志刚1,3, 梅升辉1,3, 宁霄4#, 袁晶华2,*   

  1. 1首都医科大学附属北京天坛医院药学部,北京 100050;
    2浙江树人学院树兰国际医学院,浙江 杭州 310000;
    3首都医科大学药学院,北京 100069;
    4中国食品药品检定研究院食品化妆品检定所,北京 100050
  • 收稿日期:2024-11-01 出版日期:2025-10-15 发布日期:2025-10-20
  • 通讯作者: *袁晶华,女,博士,治疗药物监测。E-mail: 601660@zjsru.edu.cn;#为共同通信作者。
  • 作者简介:刘彤彤,女,药物分析与治疗药物监测研究。
  • 基金资助:
    国家重点研发计划（2021YFC2401100）; 中国药品监督管理研究会课题基金（2023zh005）

An HPLC-MS/MS Method for Determination of Ceftazidime and Avibactam Concentrations in Human Plasma

LIU Tongtong1,3, GUO Xingchen1,3, ZHANG Dongjie1,3, CHEN Qi2, ZHAO Zhigang1,3, MEI Shenghui1,3, NING Xiao4#, YUAN Jinghua2,*   

  1. 1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
    2Shulan International Medical College of Zhejiang Shuren University, Hangzhou Zhejiang 310000, China;
    3School of Pharmacy, Capital Medical University, Beijing 100069, China;
    4Institute for Food and Cosmetics Testing, National Institutes of Food and Drug Control, Beijing 100050, China
  • Received:2024-11-01 Online:2025-10-15 Published:2025-10-20

PDF (PC)

58

增强发表(附录)

1

摘要： 目的 建立经过验证的人血浆中头孢他啶（Ceftazidime,CAZ）和阿维巴坦（Avibactam,AVI）浓度测定的液质联用方法,并应用于临床样本测定。方法 血浆样品采用甲醇沉淀蛋白法,分别以CAZ-d6、AVI-13C5为内标（IS）。采用ProChrom300 C18柱（谱胜科技,2.1 mm×50 mm, 3μm粒径）,0.1%甲酸水和0.1%甲酸-甲醇梯度洗脱,流速0.3 mL·min-1,柱温40℃。CAZ在ESI+监测下定性和定量离子对为：m/z 547.0>467.7和m/z 547.0>396.0,IS定性和定量离子对为：m/z 553.0>402.0和m/z 553.0>473.7;AVI在ESI-的监测下定性和定量离子对为m/z 263.7>79.8和m/z 263.7>96.0,IS定性和定量离子对为m/z 268.7>79.8和m/z 268.7>96.0。结果 CAZ浓度在2.00~200.30μg·mL-1线性良好,日内和日间准确度为-5.64%~3.79%和-7.10%~-1.83%;日内和日间精密度（RSD%）为1.06%~3.34%和1.45%~6.36%;AVI浓度在0.21~20.50μg·mL-1线性良好,日内和日间准确度为5.22%~13.39%和-3.46%~5.06%;日内和日间RSD%为2.39%~3.88%和2.41%~6.23%。方法 检测CAZ低、中、高浓度下回收率在95.00%~98.50%,AVI 低、中、高浓度下回收率在96.50%~105.10%,样品在所有考察条件下均稳定。结论 本研究建立的液质联用测定CAZ和AVI血浆浓度方法准确、稳定、简便,可用于临床血药浓度监测。

关键词: 液相色谱串联质谱法, 头孢他啶, 阿维巴坦, 治疗药物监测, 血浆

Abstract: Objective To establish an LC-MS/MS method for the determination of ceftazidime (CAZ) and avibactam (AVI) in human plasma and apply the method to detection of clinical samples. Methods Plasma samples were deproteinized via methanol precipitation, with CAZ-d6 and AVI-13C5 as internal standards (IS), respectively. Chromatographic separation was performed on a ProChrom300 C18 column (Pusheng Technology, 2.1 mm×50 mm, 3 μm particle size) using gradient elution with 0.1% formic acid in water and in methanol respectively. The flow rate was 0.3 mL·min-1 and the column temperature was 40°C. For CAZ under the ESI+ mode, the qualitative and quantitative ion pairs were m/z 547.0>467.7 and m/z 547.0>396.0, respectively while the corresponding ion pairs for its IS were m/z 553.0>402.0 and m/z 553.0>473.7, compared with m/z 263.7>79.8 and m/z 263.7>96.0 respectively and m/z 268.7>79.8 and m/z 268.7>96.0 respectively for AVI-under ESI-. Results CAZ showed good linearity over the range of 2.00 μg·mL-1 to 200.30 μg·mL-1. The intra-day and inter-day accuracies were -5.64% to 3.79% and -7.10% to -1.83%, respectively while the intra-day and inter-day precisions (RSD%) were 1.06% to 3.34% and 1.45% to 6.36%, respectively, compared with 0.21 μg·mL-1 to 20.50 μg·mL-1, -5.22% to 13.39% and -3.46% to 5.06%, and 2.39% to 3.88% and 2.41% to 6.23% for AVI. The recovery rates of CAZ at low, medium and high concentrations ranged from 95.00% to 98.50%, compared with 96.50% to 105.10% for AVI. Samples remained stable under all tested conditions. Conclusion The established LC-MS/MS method for the determination of plasma CAZ and AVI is accurate, stable, simple, and suitable for clinical monitoring of therapeutic drugs.

Key words: HPLC-MS/MS, Ceftazidime, Avibactam, Therapeutic Drug Monitoring, Plasma

中图分类号: