SENSITIVE, SPECIFIC QUANTITATIVE-ANALYSIS OF TACROLIMUS (FK506) IN BLOOD BY LIQUID-CHROMATOGRAPHY ELECTROSPRAY TANDEM MASS-SPECTROMETRY

The capacity of liquid chromatography-tandem mass spectrometry (LC-MS( 2)) to detect and define individual components in a complex mixture ha s been utilized to develop a quantitative assay of the potent immunosu ppressant drug, tacrolimus. Trough blood concentrations were measured in 175 samples obtained over several weeks after liver transplantation from seven patients. The assay was linear dyer the range of 0.2 to 10 0 mu g/L. Imprecision was <8%, and accuracy was 99-101%. The turnaroun d time for a batch of 20 samples was 2.5 h. No interference from any o f the other drug being administered to the patients was evident. An EL ISA also performed on the same samples overestimated the concentration s substantially, as indicated by a plot of the difference between the results for the two methods vs their mean. The favorable characteristi cs of the LC-MS(2) assay, especially its sensitivity and specificity, will facilitate detailed pharmacokinetic studies of tacrolimus, partic ularly under circumstances in which metabolism is perturbed by either hepatic dysfunction or drug interactions.