Comparison of Plasma Voriconazole Concentration Using LC-MS/MS and CLIA

OBJECTIVE  To evaluate the difference, correlation and consistency of the results of voriconazole concentration in human plasma determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS) and chemiluminescence immunoassay(CLIA), so as to provide a reference for clinical monitoring of voriconazole blood concentration and individualized medication.

METHODS  Blood samples of 153 patients were collected after voriconazole blood concentration reached steady state, and plasma was obtained after centrifugation. The voriconazole blood concentration was determined by LC-MS/MS and CLIA, respectively, and the results of the 2 methods were statistically analyzed.

RESULTS  The voriconazole concentration measured by CLIA was 4.61(2.95, 6.67) μg·mL⁻¹, which was lower than that by LC-MS/MS, which was 4.85(3.44, 6.66) μg·mL⁻¹. And the Wilcoxon paired test showed that the difference was statistically significant(Z=–4.175, P<0.001). The Spearman correlation analysis showed that the correlation coefficient between the blood concentrations of voriconazole measured by CLIA and LC-MS/MS was 0.970(P<0.01). The Passing-Bablok regression analysis showed that the regression equation of CLIA and LC-MS/MS for detection of voriconazole blood concentration was C_CLIA=–0.436+1.035C_LC-MS/MS. The Bland-Altman scatter plot analysis showed that 5.23%(8/153) of the difference of voriconazole concentration measured by CLIA and LC-MS/MS was outside the consistency limit (±1.96 SD). The difference between the 2 methods corresponding to the top of the mountain plot also tended to 0. Kappa analysis showed that the clinical compliance rate of voriconazole blood concentration detected by CLIA and LC-MS/MS was 94.12%(144/153), and the consistency coefficient Kappa=0.884.

CONCLUSION  The blood concentrations of voriconazole determined by CLIA and LC-MS/MS show good correlation and consistency, but the results of CLIA are generally lower than those of LC-MS/MS. Therefore, when different methods are used to determine the blood concentration of voriconazole in clinical practice, the differences between these methods should be paid attention to and corresponding adjustments should be made.