Rapid and simultaneous determination of tacrolimus (FK506) and diltiazem in human whole blood by liquid chromatography-tandem mass spectrometry: application to a clinical drug-drug interaction study

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Jia Li LiShufeng Zhou

Abstract

Tacrolimus (FK506) is a potent immunosuppressant widely used for organ transplantation patients while diltiazem (DTZ), a calcium-channel inhibitor, is often used in renal transplantation patients to prevent post-transplant hypertension. However, DTZ has a significant pharmacokinetic interaction with FK506. In this study, a rapid and sensitive ammonium-adduct based liquid chromatography-tandem mass spectrometry (LC/MS/MS) method has been developed and validated for the simultaneous determination of FK506 and DTZ in human whole blood using ascomycin as the internal standard (IS). After extraction of the whole blood samples by ethyl acetate, FK506, DTZ and the IS were subjected to LC/MS/MS analysis using electro-spray positive-ion mode ionization (ESI(+)). Chromatographic separation was performed on a Hypersil BDS C18 column (50 mm x 2.1 mm, i.d., 3 microm). The MS/MS detection was conducted by monitoring the fragmentation of 821.7-->768.9 (m/z) for FK506, 415.5-->310.3 (m/z) for DTZ and 809.8-->757.0 (m/z) for IS. The method had a chromatographic running time of approximately 2 min and linear calibration curves over the concentrations of 0.5-200 ng/mL for FK506 and 2-250 ng/mL for DTZ. The recoveries of liquid-liquid extraction m...Continue Reading

Citations

Jan 28, 2014·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xiao-ling QinHui-chang Bi
Dec 25, 2012·Journal of Chromatographic Science·Vivek UpadhyayPranav S Shrivastav
Dec 23, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Chun-Yun ChenXiao-Dong Wen
Jun 15, 2010·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Kazuyoshi NozakiRyuichi Arakawa
Mar 13, 2012·Therapeutic Drug Monitoring·Ilse R DubbelboerOlof Beck

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