New liquid chromatography-tandem mass spectrometry method for routine TDM of vancomycin in patients with both normal and impaired renal functions and comparison with results of polarization fluoroimmunoassay in light of varying creatinine concentrations

A new LC-MS/MS method with simple sample extraction and a relatively short period of vancomycin analysis for routine therapeutic drug monitoring was developed and validated. 50 mu L serum was precipitated using 20 mu L 33% trichloroacetic acid and 0.5 mol/L NH4OH was added to increase pH before analysis. A RP BEH C18, 1.7 mu m, 2.1 x 50 mm column maintained at 30 degrees C and tobramycin as internal standard were used. Mass detection was performed in positive electrospray mode. The results obtained with LC-MS/MS method were correlated with an FPIA assay (Abbott AxSYM) using mouse monoclonal antibody. Subjects were divided into three groups according to creatinine levels (53.5 +/- 19.1, 150.2 +/- 48.4, 471.7 +/- 124.7 mu mol/L) and Passing-Bablok regression analysis and Bland Altman analysis were used to compare vancomycin concentrations. The results of subjects with both normal and higher creatinine levels correlated very well and the linear regression model equations were near ideal (LC-MSVAN = 0.947 x Abbott(VAN) + 0.192 and LC-MSVAN = 0.973 x Abbott(VAN) - 0.411 respectively). Dialyzed patients with the highest creatinine levels showed about 14% greater vancomycin concentration with the FPIA assay (LC-MSVAN = 0.866 x Abbott(VAN) + 2.127). This overestimation probably due to the presence of the metabolite CDP ought not to be of clinical relevance owing to the wide range of recommended vancomycin concentration.