Development and validation of an UPLC–MS/MS assay for the simultaneous quantification of seven commonly used antibiotics in human plasma and its application in therapeutic drug monitoring

Author:

Mekking Xin Meng1,Velthoven-Graafland Kirsten2,Teulen Marga J A2,Brüggemann Roger J M2ORCID,te Brake Lindsey H M2,Jager Nynke G L2ORCID

Affiliation:

1. School of Pharmacy, Utrecht University , Leuvenlaan 4, 3584 CE, Utrecht , The Netherlands

2. Department of Pharmacy, Radboud Institute for Medical Innovation, Radboud University Medical Centre , Geert Grooteplein Zuid 10, 6525 GA Nijmegen , The Netherlands

Abstract

Abstract Objective To develop and validate an UPLC–MS/MS assay for simultaneous determination of the total concentration of ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, tazobactam, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim, and the protein-unbound concentration of flucloxacillin, in human plasma to be used for research and clinical practice. Methods Sample pretreatment included protein precipitation with methanol. For the measurement of protein-unbound flucloxacillin, ultrafiltration was performed at physiological temperature. For all compounds, a stable isotopically labelled internal standard was used. Reliability of the results was assessed by participation in an international quality control programme. Results The assay was successfully validated according to the EMA guidelines over a concentration range of 0.5–100 mg/L for ceftazidime, 0.05–10 mg/L for ciprofloxacin, 0.4–125 mg/L for flucloxacillin, 0.2–60 mg/L for piperacillin, 0.15–30 mg/L for tazobactam, 1–200 mg/L for sulfamethoxazole and N-acetyl sulfamethoxazole, 0.05–10 mg/L for trimethoprim and 0.10–50 mg/L for unbound flucloxacillin. For measurement of total concentrations, the within- and between-day accuracy ranged from 90.0% to 109%, and 93.4% to 108%, respectively. Within- and between-day precision (variation coefficients, CVs) ranged from 1.70% to 11.2%, and 0.290% to 5.30%, respectively. For unbound flucloxacillin, within-day accuracy ranged from 103% to 106% and between-day accuracy from 102% to 105%. The within- and between-day CVs ranged from 1.92% to 7.11%. Results of the international quality control programme showed that the assay is reliable. Conclusions The method provided reliable, precise and accurate measurement of seven commonly prescribed antibiotics, including the unbound concentration of flucloxacillin. This method is now routinely applied in research and clinical practice.

Publisher

Oxford University Press (OUP)

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3