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LC-MS/MS-based multiplex antibacterial platform for therapeutic drug monitoring in intensive care unit patients
Liang Liu1, Liu Zhang1, Xiangyi Zheng1
1Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
Abstract:
Empirically prescribed standard dosing regimens of antibacterial agents may result in insufficient or excess plasma concentrations with persistently poor clinical outcomes, especially for patients in intensive care units (ICUs). Therapeutic drug monitoring (TDM) of antibacterial agents can guide dose adjustments to benefit patients. In this study, we developed a robust, sensitive, and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform for the quantification of 14 antibacterial and antifungal agents (beta-lactams piperacillin, cefoperazone, and meropenem; beta-lactamase inhibitors tazobactam and sulbactam; antifungal agents fluconazole, caspofungin, posaconazole, and voriconazole; and daptomycin, vancomycin, teicoplanin, linezolid, and tigecycline) that can be used for patients with severe infection. This assay requires only 100 µL of serum with rapid protein precipitation. Chromatographic analysis was performed using a Waters Acquity UPLC C8 column. Three stable isotope-labeled antibacterial agents and one analogue were used as internal standards. Calibration curves ranged from 0.1-100 μg/mL, 0.1-50 μg/mL, and 0.3-100 μg/mL for different drugs, and all correlation coefficients were greater than 0.9085. Intra- and inter-day imprecision and inaccuracy values were below 15%. After validation, this new method was successfully employed for TDM in routine practice.
Insights
Standard antibacterial dosing can fail in intensive care units (ICUs). This study presents a new LC-MS/MS method for therapeutic drug monitoring (TDM) of 14 agents, improving patient outcomes.
Area of Science:
- Clinical Chemistry
- Analytical Chemistry
- Pharmacology
Background:
- Standard antibacterial dosing in intensive care units (ICUs) often leads to suboptimal drug concentrations and poor patient outcomes.
- Therapeutic drug monitoring (TDM) is crucial for optimizing antibacterial dosing in critically ill patients.
Purpose of the Study:
- To develop and validate a robust, sensitive, and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform for quantifying 14 antibacterial and antifungal agents.
- To enable precise TDM for patients with severe infections.
Main Methods:
- Quantification of 14 antibacterial and antifungal agents using LC-MS/MS with a 100 µL serum sample.
- Utilized a Waters Acquity UPLC C8 column and stable isotope-labeled internal standards.
- Validated calibration curves (0.1-100 μg/mL) and demonstrated imprecision/inaccuracy below 15%.
Main Results:
- Successfully developed a sensitive and robust LC-MS/MS assay for 14 critical antimicrobial agents.
- Achieved high correlation coefficients (>0.9085) across various calibration ranges.
- Demonstrated excellent assay precision and accuracy, suitable for clinical application.
Conclusions:
- The validated LC-MS/MS method provides a reliable tool for TDM of multiple antibacterial and antifungal agents.
- This platform can guide antimicrobial dose adjustments, potentially improving clinical outcomes in severe infections.
- The method's simplicity and low sample volume requirement facilitate its routine use in clinical practice.
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