Development and application of a simple LC-MS/MS method for therapeutic drug monitoring to guide colistin dosing in critically Ill patients.

OBJECTIVES

This study aims to develop a simple, rapid, and cost-effective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining the concentration of colistin in human serum, including its two active components, colistin A and colistin B, to support routine therapeutic drug monitoring (TDM).

METHODS

Protein precipitation was performed using pure acetonitrile, with polymyxin B1 as the internal standard (IS). Chromatographic separation was achieved using a Phenomenex KINETEX XB-C18 column (2.6 μm, 3 × 50 mm) with a gradient elution system consisting of 0.1% formic acid (FA) in water and pure acetonitrile as the mobile phase. Detection was carried out using an electrospray ionization (ESI) source in positive ion mode with multiple reaction monitoring (MRM). After applying the validated method to critically ill patients for approximately one year, we used the receiver operating characteristic (ROC) curve to identify the preliminary cut-off value of colistin trough concentration for predicting acute kidney injury (AKI).

RESULTS

The total runtime for chromatographic separation and mass spectrometric detection was 5 min. Excellent linearity was achieved over the concentration range of 0.27-8.69 µg/mL for colistin A and 0.08-2.56 µg/mL for colistin B, with R2 greater than 0.99 for both analytes. The method demonstrated acceptable matrix effects and recovery rates. In addition‌, the ROC curve analysis of colistin TDM in critically ill patients determined a preliminary cut-off value for AKI at a trough concentration of 2.22 µg/mL.

CONCLUSION

The validated method enables simultaneous and precise quantification of the two active substances, with a simple procedure and minimal analytical cost. The utility of TDM in critically ill patients is paramount for individualizing dosing regimens to optimize outcomes and safety. Specifically, the correlation between trough concentration and AKI risk highlights the importance for clinicians to monitor renal function during colistin treatment to prevent drug-induced AKI.

CLINICAL TRIAL NUMBER: Not applicable.