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

• Published in: Hong Kong journal of nephrology Vol. 7; no. 2; pp. 65 - 69
• Main Authors: Chan, Yiu-Han, Ho, Chung-Shun, Shek, Chi-Chung, Wong, Kim-Ming, Chak, Wai-Leung, Choi, Koon-Shing, Chau, Ka-Foon, Li, Chun-Sang
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2005
• Subjects: drug concentration; HPLC-MS/MS; kidney transplant; MEIA; tacrolimus; kidney transplant; HPLC-MS/MS; MEIA; tacrolimus; drug concentration
• ISSN: 1561-5413; 1876-4371
• DOI: 10.1016/S1561-5413(09)60216-7

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.
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 (AUC
12) 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 AUC
12 values calculated by the two methods were highly correlated (
r = 0.90;
p < 0.0005). The mean difference between the AUC
12 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.
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 AUC
12 level estimated by our abbreviated regression equation.