LC-MS/MS Method for Simultaneous Quantification of Three Oxazolidinone Antimicrobials in Human Plasma: Application to Therapeutic Drug Monitoring.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-10-01 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S547979

Na Zhang, Nan Bai, Ying Wang, Beibei Liang, Yun Cai

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引用次数: 0

Abstract

Background: Oxazolidinone antimicrobials, which are effective against multidrug-resistant gram-positive pathogens, face challenges of variable efficacy and safety owing to patient pharmacokinetic differences.

Purpose: This study aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to simultaneously quantify multiple oxazolidinone antimicrobials, including linezolid, tedizolid, and contezolid, for therapeutic drug monitoring (TDM) applications.

Methods: Chromatographic separation was achieved on a C18 column (100 × 2.1 mm, 3.5 μm) with gradient elution. Detection was performed via positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, targeting transitions: m/z 338.14→162.8 (linezolid); m/z 371→343.1 (tedizolid) and m/z 409.15→269.14 (contezolid), with voriconazole-d3 as the internal standard.

Results: The method was validated using Bioanalytical Method Validation (M10). The method demonstrated high selectivity and wide linear ranges of 50.0-15,000.0 ng/mL for linezolid and contezolid, and 25.0-7500.0 ng/mL for tedizolid, respectively, with a good linearity (R² > 0.993). The intra- and inter-day accuracy and precision were within acceptable limits. Recovery ranged from 94.4% to 104.2% in plasma, and matrix effects were negligible (CV%<3.6%). Stability experiments confirmed analyte integrity under short-term (8 h at room temperature), long-term (34 days at -80°C for linezolid; 40 days for tedizolid and contezolid), and freeze-thaw conditions. No carry-over contamination was exhibited. This method has been successfully applied to monitor the concentrations of both drugs during the transition between linezolid and contezolid therapy.

Conclusion: This validated LC-MS/MS method enables the simultaneous determination of linezolid, tedizolid, and contezolid in human plasma, rendering it promising for pharmacokinetic studies and TDM, and contributing to optimized patient care in complex therapeutic scenarios.

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LC-MS/MS法同时定量人血浆中三种恶唑烷酮类抗菌药：在治疗药物监测中的应用。

背景：恶唑烷酮类抗菌药物对多重耐药革兰氏阳性病原体有效，但由于患者药代动力学差异，其疗效和安全性存在差异。目的：建立一种液相色谱-串联质谱（LC-MS/MS）同时定量治疗药物监测（TDM）中恶唑烷酮类药物利奈唑胺、替地唑胺和康替唑胺的方法。方法：采用C18色谱柱（100 × 2.1 mm, 3.5 μm）进行梯度洗脱。在多反应监测（MRM）模式下，通过正电喷雾电离（ESI+）进行检测，目标转变为：m/z 338.14→162.8（利奈唑胺）；M /z 371→343.1 （tedizolid）和M /z 409.15→269.14 (contezolid)，以伏立康唑-d3为内标。结果：采用生物分析方法验证（M10）对方法进行了验证。该方法选择性高，线性范围宽，对利奈唑胺和康替唑胺分别为50.0 ~ 15000 0.0 ng/mL，对泰地唑胺为25.0 ~ 7500.0 ng/mL，线性关系良好（R2为0 0.993）。日内、日间的准确度和精密度均在可接受范围内。结论：经验证的LC-MS/MS方法可同时测定人血浆中利奈唑胺、泰地唑胺和康替唑胺，为药代动力学研究和TDM提供了良好的应用前景，有助于在复杂的治疗方案中优化患者护理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.