Related Experiment Video
Updated: Apr 29, 2026
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Analytical Considerations and Often-Overlooked Aspects in the Therapeutic Drug Monitoring of Polymyxins in Human
Mengdan Liu1,2, Zhilong Yuan1, Jun Chen3
1Department of Pharmacy, Shanghai Changhai Hospital, the First Affiliated Hospital of Naval Medical University, Shanghai, China.
Abstract:
Therapeutic drug monitoring (TDM) of polymyxins is paramount for optimizing efficacy and minimizing toxicity in the treatment of multidrug-resistant Gram-negative infections. However, accurate quantification via liquid chromatography-tandem mass spectrometry (LC-MS/MS) is compromised by a series of often-overlooked yet critical analytical challenges. This comprehensive review identifies and addresses three major pre-analytical and analytical pitfalls: (1) the inherent variability in compositional heterogeneity and the salt form of commercial standards, which we propose to correct using a batch-specific weighted average molecular weight formula;(2) significant nonspecific adsorption（NSA） to laboratory surfaces, requiring proactive mitigation strategies such as silanization and additive use; (3) the pronounced and pH-dependent instability of colistimethate sodium (CMS), which necessitates strict non-acidic sample preparation protocols to prevent artificial hydrolysis; Furthermore, we clarify the clinical contexts for measuring active versus total colistin concentrations. By synthesizing current evidence and offering practical methodological refinements, this work aims to enhance the accuracy, reproducibility, and clinical utility of polymyxins TDM, ultimately supporting more precise dosing and improved patient.
Insights
Accurate therapeutic drug monitoring (TDM) for polymyxins requires addressing analytical challenges. This review details methods to improve the precision and reliability of polymyxin TDM for better patient outcomes.
Area of Science:
- Analytical Chemistry
- Pharmacology
- Clinical Pharmacy
Background:
- Therapeutic drug monitoring (TDM) of polymyxins is crucial for treating multidrug-resistant Gram-negative infections.
- Accurate quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS) faces significant analytical hurdles.
Purpose of the Study:
- To identify and address pre-analytical and analytical challenges in polymyxin TDM.
- To enhance the accuracy, reproducibility, and clinical utility of polymyxin TDM.
Main Methods:
- Review of current evidence on polymyxin TDM analytical challenges.
- Proposal of methodological refinements including a weighted average molecular weight formula for standards, mitigation strategies for nonspecific adsorption (NSA), and non-acidic sample preparation for colistimethate sodium (CMS) stability.
- Clarification of clinical contexts for measuring active versus total colistin concentrations.
Main Results:
- Identified three major pitfalls: variability in commercial standards, nonspecific adsorption (NSA) to lab surfaces, and pH-dependent instability of CMS.
- Proposed solutions: batch-specific weighted average molecular weight, silanization/additives for NSA, and non-acidic sample prep for CMS.
- Differentiated clinical relevance of active vs. total colistin measurements.
Conclusions:
- Addressing these analytical challenges is essential for accurate polymyxin TDM.
- Methodological refinements can improve precision and reproducibility.
- Enhanced TDM supports more precise dosing and improved patient outcomes in treating resistant infections.
More Related Videos
Related Concept Videos
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
01:16Therapeutic Drug Monitoring: Overview and Classification
01:29Therapeutic Drug Monitoring: Affecting Factors