Validation of a Liquid Chromatography-Mass Spectrometric Assay for Tacrolimus in Liver Biopsies After Hepatic Transplantation: Correlation With Histopathologic Staging of Rejection

• DOI: 10.1097/ftd.0b013e31805c73f1
• Publication Date: 2007-05-25T04:34:53Z
• Authors: Arnaud Capron; Jan Lerut; Catherine Verbaan...; Jules Mathys; Olga Ciccarelli; Roger Vanbinst; Francine Roggen; Chantal De Reyck; Julien Lemaire; Pierre E Wallemacq
• Keywords: Immunosuppression

The aims of this work were both to validate a sensitive and specific method quantify tacrolimus (TAC) in liver biopsies after hepatic transplantation evaluate the predictive value either tissue or blood TAC concentrations for rejection 146 adult patients under TAC-based immunosuppression. Trough levels monitored daily during hospital stay by immunoassay. Liver routinely performed at day 7 posttransplantation. assay was developed liquid chromatography-mass spectrometry. limit quantification 5 pg/mg, with intra- interassay precision ranging from 3.9% 14.3% 4.7% 15.9%, respectively. extraction efficiency approximately 80%. found ranged less than up 387 pg/mg. Blood 2.7 19.3 ng/mL. Tissue displayed excellent correlation histopathologic BANFF score, whereas did not. Clinically significant rejections (BANFF scores ≥6) characterized mean concentration 13.1 pg/mg 7.6 ng/mL, respectively, these values became, 74.9 (P < 0.05) 7.1 ng/mL (not significant) nonclinically episodes <6). In study, distributed wider range significantly better severity organ predose levels. A 30 is 89% 98% discriminate clinically cellular rejection. Further studies are required understand factors affecting distribution within (such as carrier proteins cytochrome genetic polymorphism, function, age, flow, type transplanted, time posttransplantation) define its treatment allograft