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

Year: 2025

Type: article

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: > 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.

Source: Drug Design Development and Therapy

DOI: 10.2147/dddt.s547979

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

Institutions: Chinese PLA General Hospital, Medical Supplies Center

Language: English

Topic: Analytical Methods in Pharmaceuticals

Subfield: Analytical Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836