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Updated: Mar 8, 2026
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Quantification of meropenem in human plasma by HILIC - tandem mass spectrometry
Jens Martens-Lobenhoffer1, Stefanie M Bode-Böger1
1Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany.
Abstract:
Meropenem is a substance from the carbapenem class of antibiotics. It is widely used in intensive care units to treat a broad range of severe bacterial infections. In this critically ill patient group therapeutic drug monitoring (TDM) is highly advisable in order to avoid under- as well as over-dosing. Here, we describe a HILIC-MS/MS method for the quantification of meropenem in human plasma which is suitable for TDM. After simple protein precipitation, the polar analyte was chromatographically separated by the HILIC mechanism on a silica based stationary phase with polyethylenimide coating. The calibration was linear over the range of 1-50μg/ml. The stable isotope labelled internal standard led to matrix independency of the quantification and to very good precision (relative standard deviations less than 5%) and accuracy (deviations from the expected values less than 4%). A cross-validation with a validated and established HPLC-UV method confirmed the accuracy of the HILIC-MS/MS method in real patient samples.
Insights
A new HILIC-MS/MS method accurately quantifies meropenem in plasma for therapeutic drug monitoring (TDM). This method ensures optimal dosing for critically ill patients, preventing under- or over-dosing of this vital antibiotic.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Clinical Pharmacy
Background:
- Meropenem, a carbapenem antibiotic, is crucial for treating severe bacterial infections in intensive care units.
- Therapeutic drug monitoring (TDM) is essential for critically ill patients to optimize meropenem dosing and prevent adverse events.
Purpose of the Study:
- To develop and validate a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for quantifying meropenem in human plasma.
- To establish a reliable method for TDM of meropenem in critically ill patients.
Main Methods:
- A HILIC-MS/MS assay was developed using a silica-based stationary phase with polyethylenimine coating for meropenem separation.
- Protein precipitation was used for sample preparation, followed by quantification using a stable isotope-labeled internal standard.
- The method was validated for linearity, precision, accuracy, and matrix effects.
Main Results:
- The HILIC-MS/MS method demonstrated linearity over a concentration range of 1-50 μg/ml.
- Excellent precision (RSD < 5%) and accuracy (bias < 4%) were achieved, with the internal standard ensuring matrix independency.
- Cross-validation against an established HPLC-UV method confirmed the accuracy of the developed assay in real patient samples.
Conclusions:
- The developed HILIC-MS/MS method is suitable for therapeutic drug monitoring of meropenem in critically ill patients.
- This assay provides accurate and precise quantification, aiding in optimizing meropenem dosage and improving patient outcomes.
- The method offers a valuable tool for clinical laboratories supporting intensive care units.
