Development of a Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Teicoplanin and Its Application in Critically Ill Patients.

Abstract

Objective: Teicoplanin, a glycopeptide antibiotic, is used to treat infections caused by Gram-positive pathogens. Trough-level monitoring of teicoplanin is recommended in specific -patient populations, including critically ill patients. This study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify teicoplanin in human plasma and adapt the method to a critically ill patient sample.

Materials and methods: Teicoplanin trough levels were measured using a newly validated LC-MS/MS method. Analysis was conducted using a C18 column with an inner diameter of 2.7 μm (50.0 x 3.0 mm), and vancomycin hydrochloride was used as the internal standard. The method's run time per sample was 5.5 minutes. Non-parametric tests were used for statistical analysis. Univariate and multivariate logistic regression were performed to identify teicoplanin target attainment factors. A p-value of <0.05 was considered statistically significant.

Results: The method demonstrated linearity between 1.56-100 mg/L teicoplanin concentration and had a lower limit of detection and quantification of 0.33 mg/L and 1.00 mg/L, respectively. Precision, accuracy, recovery rate, and carry-over effects were all within acceptable limits, according to the U.S. Food and Drug Administration (FDA) guidance. Twenty patients were included in the study. The target teicoplanin trough level (≥10 mg/L) attainment rate was 50%. The patient's laboratory values did not significantly change after teicoplanin treatment (p>0.05), except for erythrocyte count, haemoglobin, and haematocrit values, which decreased significantly (p<0.05). Multivariate analysis revealed no significant factors affecting target attainment (p>0.05).

Conclusion: The LC-MS/MS assay validated in this study is high-throughput, robust, and quick enough to be implemented in clinical therapeutic drug monitoring (TDM) laboratories. More large-scale studies are needed to understand better the relationship between teicoplanin trough levels and patient-related factors.