Measurement of Whole Blood Tacrolimus Level by High Performance Liquid Chromatography Tandem Mass Spectrometry in Renal Transplant Recipients — A Single Center Perspective

Background and Methods

Measurement of whole blood tacrolimus level by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was compared with that measured by microparticle enzyme immunoassay (MEIA) in 30 renal transplant recipients.

Results

Whole blood tacrolimus concentrations measured by HPLC-MS/MS were significantly lower than those measured by MEIA, with a median difference (interquartile range, IQR) of −0.40 μg/L (2.03 μg/L) (p < 0.0005). MEIA overestimated tacrolimus concentrations by a median (IQR) of 5.04% (19.5%). There was good correlation between the two methods (r = 0.94; p < 0.0005). The Passing-Bablok regression equation was: HPLC-MS/MS (μg/L) = 0.96 (95% confidence interval, CI, 0.91-1.00) × MEIA (μg/L) −0.02 (95% CI, −0.40-0.46). Bland-Altman analysis showed that the 95% limits of agreement were 2.98 to −4.10 μg/L. The 12-hour area under the concentration curve (AUC₁₂) of tacrolimus derived using the two-point sampling equation with tacrolimus concentrations measured by HPLC-MS/MS was compared with that measured by MEIA. The AUC₁₂ values calculated by the two methods were highly correlated (r = 0.90; p < 0.0005). The mean difference between the AUC₁₂ values was 3.4 ± 11.6 hr.μg/L, and the mean percentage difference was 2.6 ± 11.4%, both of which were not statistically significant.

Conclusion

For tacrolimus concentrations within the recommended therapeutic range, the concentration measured by HPLC-MS/MS was statistically significantly lower than that measured by MEIA, but the difference was not clinically significant. Introduction of the more specific HPLC-MS/MS method does not require adjustment in the recommended tacrolimus trough concentration or the AUC₁₂ level estimated by our abbreviated regression equation.

Key words:  drug concentration , HPLC-MS/MS , MEIA , kidney transplant , tacrolimus

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