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Updated: Aug 29, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
A UPLC-MS/MS method for simultaneous determination of eight special-grade antimicrobials in human plasma and
1Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Number 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning, PR China.
Abstract:
Linezolid, vancomycin, teicoplanin, tigecycline, imipenem, meropenem, voriconazole, and micafungin are eight special-grade antimicrobials commonly used for patients with severe infections. Changes in the pharmacodynamics and pharmacokinetics of critically ill patients severely affect the efficacy of antimicrobial drugs. Therefore, conventional or standard dosing regimens do not achieve satisfactory anti-infective effects. In the current study a simple and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneously determining the concentrations of the above-mentioned eight antimicrobials in human plasma only 3 min after one-step magnetic solid phase extraction pre-treatment. Multiple-reaction monitoring and positive ion modes were used for detection. The calibration curves were established over a concentration range of 0.1-25.0 μg/mL for teicoplanin, linezolid, micafungin, voriconazole, imipenem, igecyclin, and meropenem, and 0.2-50.0 μg/mL for vancomycin; the coefficient of correlation was > 0.9971 for all the compounds. The inter- and intra-day coefficients of variation were < 6.88% at the lower limit of quantification and quality control (QC) levels (low concentration-QC, medium concentration-QC, and high-concentration QC). The UPLC-MS/MS method was successfully used for clinical therapeutic drug monitoring of linezolid, vancomycin, teicoplanin, tigecycline, imipenem, meropenem, voriconazole, and micafungin for critically ill patients.
Insights
A new UPLC-MS/MS method accurately measures eight critical antimicrobials in critically ill patients. This validated technique aids therapeutic drug monitoring for severe infections, improving patient outcomes.
Area of Science:
- Pharmacology and Clinical Pharmacy
- Analytical Chemistry
- Infectious Diseases
Background:
- Critically ill patients exhibit altered pharmacokinetics and pharmacodynamics, impacting antimicrobial efficacy.
- Standard dosing regimens may be insufficient for severe infections in this population.
- Therapeutic drug monitoring (TDM) is crucial for optimizing antimicrobial therapy.
Purpose of the Study:
- To develop and validate a rapid, simultaneous UPLC-MS/MS method for eight key antimicrobials.
- To enable precise quantification of these drugs in human plasma for TDM.
- To support optimized dosing strategies in critically ill patients.
Main Methods:
- Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed.
- A single-step magnetic solid-phase extraction (MSPE) was used for sample preparation.
- Multiple-reaction monitoring (MRM) in positive ion mode facilitated detection.
Main Results:
- The validated UPLC-MS/MS method achieved a rapid 3-minute sample analysis time.
- Excellent linearity (R² > 0.9971) and low coefficients of variation (< 6.88%) were demonstrated.
- The method successfully quantified linezolid, vancomycin, teicoplanin, tigecycline, imipenem, meropenem, voriconazole, and micafungin.
Conclusions:
- The developed UPLC-MS/MS method is simple, specific, and efficient for simultaneous TDM.
- This assay provides a valuable tool for optimizing antimicrobial therapy in critically ill patients.
- Accurate drug concentration measurements can lead to improved clinical outcomes and reduced antimicrobial resistance.
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