Determination of linezolid in critically ill patients plasma by LC-MS/MS

OBJECTIVE To develop an LC-MS/MS method for determination of linezolid in critically ill patients plasma and applied to drug monitoring. METHODS The plasma samples were precipitated with acetonitrile, with D3-linezolid as an internal standard. The separation was achieved on ZORBAX SB C₁₈column (2.1 mm×100 mm, 3.5 μm) and eluted with linear gradient using acetonitrile and water (both of containing 0.1% formic acid) at the flow rate of 0.30 mL·min^-1, the injection volume was 5 μL and the column temperature was 30℃. The total time of the analysis was 4.0 min. Detection of the analytes were achieved using positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. RESULTS The linear calibration curve of linezolid obtained concentration range of 0.10-20.0 mg·mL^-1(r>0.99), with the lower limit of quantitation of 0.10 mg·mL^-1. The accuracy of linezolid was within 93.3%-106.7%, intra-day and inter-day relative standard deviations were both <15%. The extraction recoveries ranged 74.9%-85.1%. CONCLUSION The established method is rapid, sensitive, accurate, specific and reliable, and suitable for the study of therapeutic drug monitoring of linezolid.