Analysis of whole blood tacrolimus concentrations in liver transplant patients exhibiting impaired liver function

In transplant patients with impaired Liver function, HPLC methodologies hav e been suggested for monitoring whole blood tacrolimus concentrations becau se of the reported inaccuracy of immunoassay for whole blood tacrolimus con centrations. One hundred fifty whole blood samples from 50 subjects enrolle d in a multicenter liver transplant trial were chosen for HPLC/MS/MS analys is without consideration of the clinical status of the patient at the time of sampling. These samples were chosen to represent the sampling intervals during the 12-week posttransplantation period. Retrospectively, the authors identified a subset of 39 samples from 27 subjects exhibiting impaired liv er function as demonstrated by bilirubin concentrations > 3.0 mg/dL (mean /- SD = 7.5 +/- 5.6 mg/dL), The authors compared the agreement of concentra tions obtained from the PRO-Trac II ELISA and HPLC/MS/MS by least squares l inear regression analysis and Bland/Altman analysis, in this subset against the agreement of concentrations for 76 samples with normal bilirubin. In t he samples obtained from patients with impaired liver function the resultin g regression equation was: ELISA = 1.19(HPLC) + 0.7; r = 0.9. The mean diff erence (HPLC/MS/MS - ELISA) was -2.5 ng/mL +/- 2.9 ng/mL (mean +/- SD). Whi le 71% of samples agreed within 3 ng/mL, 3% (n = 1) exhibited a difference >10 ng/ml. The corresponding evaluation of the samples with normal bilirubi n concentrations resulted in the regression equation ELISA = 0.96(HPLC) + 0 .9; r = 0.9, and a mean difference of -0.6 ng/mL +/- 2.3 ng/mL. The authors conclude that while a small subset of patients with cholestasis may requir e closer evaluation with a more specific methodology, the majority of the p atients may be satisfactorily monitored with the PRO-Trac II ELISA.