Arzneimittelforschung 2007; 57(10): 659-664
DOI: 10.1055/s-0031-1296665
Immunomodulators · Immunostimulants · Immunosuppressants
Editio Cantor Verlag Aulendorf (Germany)

Development of an Ultra-performance Liquid Chromatography Technique Coupled with Mass Spectrometry for the Measurement of Tacrolimus in Micro-samples of Whole Blood, and its Application on a Pharmacokinetic Trial

Gabriel Marcelín-Jiménez
1  Servicio de InvestigaciɃn de Farmacologȷa Clȷnica, Hospital General de Mȳxico, Mexico City, Mexico
,
Alberto García-González
1  Servicio de InvestigaciɃn de Farmacologȷa Clȷnica, Hospital General de Mȳxico, Mexico City, Mexico
,
Alionka P. Ángeles-Moreno
1  Servicio de InvestigaciɃn de Farmacologȷa Clȷnica, Hospital General de Mȳxico, Mexico City, Mexico
,
Leticia Contreras-Zavala
1  Servicio de InvestigaciɃn de Farmacologȷa Clȷnica, Hospital General de Mȳxico, Mexico City, Mexico
,
Liliana Rivera
1  Servicio de InvestigaciɃn de Farmacologȷa Clȷnica, Hospital General de Mȳxico, Mexico City, Mexico
,
Miriam Morales
1  Servicio de InvestigaciɃn de Farmacologȷa Clȷnica, Hospital General de Mȳxico, Mexico City, Mexico
› Author Affiliations
Further Information

Publication History

Publication Date:
21 December 2011 (online)

Abstract

Objective: The aim was to develop a rapid, specific, sensitive and accurate chromato-graphic technique coupled with mass spectrometry for the measurement of tacrolimus (CAS 104987-11-3) in micro-samples of whole blood, and its application on a pharmacokinetic pilot trial.

Methods: A fast gradient was designed in an ultra-performance liquid chromatog-raphy, and coupled with a mass spectrometer for the quantification of tacroli-mus in 100 µl samples of EDTA whole blood. Multiple reaction monitoring was used for the measurement of tacrolimus (m/z+1 821.49→768.35 Th) and sirolimus as internal standard (m/z+1 931.69→864.39 Th). The method was validated according to Mexican regulatory guidelines. Twenty-four young healthy male volunteers with similar hematocrit values participated in the pharmacoki-netic trial; an oral single dose of one 5 mg tacrolimus capsule was administered and kinetic profiles were described since 0 h until 24 h post-dose.

Results: Method showed to be accurate, precise and linear over the range from 1 to 80 ng/ml, having an absolute recovery of 94 %. Molecule was stable for two months at –70 °C, and heparin interfered with its quantification. Total run-time is around 1.5 min. Mean maximum blood concentration was 32.63 ± 1.74 ng/ml, and was reached at 1 h post-dose; elimination half-life was 14.18 ± 5.71 h.

Conclusions: Method developed is not time-consuming, inexpensive, and sensitive enough for its application during pharmacokinetic trials, and can be suitable for therapeutic drug monitoring in transplanted patients. Pharmacokinetic data obtained in Mexican population are quite similar to previously reported in international literature.