Simultaneous determination of tedizolid and linezolid in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study

Abstract A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine tedizolid and linezolid in rat plasma simultaneously. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a XEVO TQD triple quadruple mass spectrometer coupled with an electrospray ionization (ESI) source in the positive ion mode. Multiple reaction monitoring (MRM) mode was used for quantification using target fragment ions m/z 371.4 → 343.2 for tedizolid, and m/z 338.3 → 56.1 for linezolid. This assay method has been fully validated in terms of selectivity, linearity, recovery and matrix effect, accuracy, precision and stability. The linearity of this method was found to be within the concentration range of 5–5000 ng/mL for tedizolid, and 10–10,000 ng/mL for linezolid in rat plasma, respectively. Only 3.0 min was needed for an analytical run. This assay was used to support a preclinical study where multiple oral doses were administered to rats to investigate the pharmacokinetics of tedizolid and linezolid.