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使用液相色谱-串联质谱系统对重症监护病房广泛使用的15种抗生素进行定量分析:一种进行每日治疗药物监测的简便方法。

Quantification of 15 Antibiotics Widely Used in the Critical Care Unit with a LC-MS/MS System: An Easy Method to Perform a Daily Therapeutic Drug Monitoring.

作者信息

Feliu Catherine, Konecki Celine, Candau Tristan, Vautier Damien, Haudecoeur Cyril, Gozalo Claire, Cazaubon Yoann, Djerada Zoubir

机构信息

Department of Pharmacology, HERVI, EA 3801, SFR CAP-Santé, Reims University Hospital, 51 Rue Cognacq-Jay, CEDEX, 51095 Reims, France.

Institute Desbrest of Epidemiology and Public Health, INSERM, University Montpellier, 34000 Montpellier, France.

出版信息

Pharmaceuticals (Basel). 2021 Nov 24;14(12):1214. doi: 10.3390/ph14121214.

DOI:10.3390/ph14121214
PMID:34959617
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8703964/
Abstract

Potential under- or overdose of antibiotics may occur in intensive care units due to high variability in plasma concentrations. The risk is either treatment failure or toxicity. Thus, therapeutic drug monitoring of antibiotics may guide dosing adjustment, maximising antibacterial efficacy and minimising toxicity. The aim of this study was to develop and validate a method for the analysis of 15 antibiotics including beta-lactams, linezolid, fluoroquinolones, daptomycin, and clindamycin to have a complete panel in the management of infections. We proposed to develop a fast, sensitive, and quantitative method for the analysis of 15 antibiotics using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS) technology. this method required only 100 µL of plasma and consisted of a rapid liquid-liquid deproteinisation using methanol. Calibration curves ranged from 0.078 to 500 mg/L depending on the molecules, and were defined according to a therapeutic range. Inter- and intra-assay precisions values were less than 15%. This work described the development and the full validation of a precise, sensitive and accurate assay using UPLC-MS/MS technology. After validation, this new assay was successfully applied to routine therapeutic drug monitoring.

摘要

由于血浆浓度变化很大,重症监护病房可能会出现抗生素潜在的用药不足或过量情况。风险要么是治疗失败,要么是毒性反应。因此,抗生素治疗药物监测可指导剂量调整,使抗菌疗效最大化并将毒性最小化。本研究的目的是开发并验证一种用于分析15种抗生素的方法,这些抗生素包括β-内酰胺类、利奈唑胺、氟喹诺酮类、达托霉素和克林霉素,以便在感染管理中有一套完整的检测项目。我们提议开发一种快速、灵敏且定量的方法,使用超高效液相色谱-串联三重四极杆质谱仪(UPLC-MS/MS)技术分析这15种抗生素。该方法仅需100μL血浆,且包括使用甲醇进行快速液-液脱蛋白处理。校准曲线根据不同分子在0.078至500mg/L范围内,且根据治疗范围来定义。批间和批内精密度值均小于15%。这项工作描述了使用UPLC-MS/MS技术进行的一种精确、灵敏且准确的检测方法的开发及全面验证。验证后,这种新检测方法成功应用于常规治疗药物监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/8703964/049d7f0fbd80/pharmaceuticals-14-01214-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/8703964/27ad80bce8b5/pharmaceuticals-14-01214-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/8703964/bb94d49e3d77/pharmaceuticals-14-01214-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/8703964/049d7f0fbd80/pharmaceuticals-14-01214-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/8703964/27ad80bce8b5/pharmaceuticals-14-01214-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/8703964/bb94d49e3d77/pharmaceuticals-14-01214-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112b/8703964/049d7f0fbd80/pharmaceuticals-14-01214-g003.jpg

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