Measurement of teicoplanin by liquid chromatography-tandem mass spectrometry: Development of a novel method

Abstract

Background: Teicoplanin is an antibiotic used for the treatment of endocarditis, osteomyelitis, septic arthritis and methicillinresistant Staphylococcus aureus. Teicoplanin is emerging as a suitable alternative antibiotic to vancomycin, where their trough serum levels are monitored by immunoassay routinely. This is the first report detailing the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring teicoplanin in patients' serum. Methods: An Acquity™ UPLC (ultra-pressure liquid chromatography) tandem mass spectrometer was used to measure teicoplanin concentrations in samples from patients, quality assurance schemes and quality control preparations. Ristocetin was successfully implemented as a suitable internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of quantification and detection, interference and method comparison against immunoassay were all assessed. Results: Teicoplanin and ristocetin had elution times of 1.39 and 1.24 min, respectively. Ion suppression was shown to be negligible, and linear calibration curves (0-200 μg/mL) were consistently reproduced to have r2 values >0.99. Postextraction stability was achieved up to 20 h, while matrix effects were minimal coupled with sample recovery of >93%. The lower limit of quantification was 1 μg/mL, and 0.2 μg/mL was the lower limit of detection. Interference with other antibiotics was dependent on the combination of drugs present in patients' serum. A method comparison between immunoassay and LCMS/MS suggested a negative bias for tandem mass spectrometry. Conclusions: This novel method of teicoplanin determination by LC-MS/MS is proven to be a robust protocol that is consistent and reproducible. Clinicians searching for alternatives in therapeutic drug monitoring may have an additional option that is potentially more accurate and specific.