Developing an isotope dilution UHPLC-MS/MS method to quantify linezolid in human plasma: application to therapeutic...

Aim: To optimize clinical efficacy and reduce the drug-exposure-related toxicity of linezolid, whose concentrations show wide inter-variabilities, a simple and reliable quantitative assay for therapeutic drug monitoring is necessary. Results: A UHPLC-MS/MS assay has been established for determination of linezolid in human plasma and fully validated according to the US FDA guidelines. After a simple, isotope-dilluted precipitation with methanol, the analytes were separated by a straightforward isocratic mode and the MS/MS was conducted under the ESI⁺ mode fitted with SRM. The calibration curves proved acceptable linearity in the range of 0.1-30.0 µg/ml. Conclusion: The present assay is currently used in routine clinical practice, being applied to therapeutic drug monitoring and helps to optimize individual dosing regimens and manage adverse effects in ICU patients.