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-MS2) to detect and define individual components in a complex mixture has been utilized to develop a quantitative assay of the potent immunosuppressant drug, tacrolimus. Trough blood concentrations were measured in 175 samples obtained over several weeks after liver transplantation from seven patients. The assay was linear over the range of 0.2 to 100 micrograms/L. Imprecision was <8%, and accuracy was 99-101%. The turnaround time for a batch of 20 samples was 2.5 h. No interference from any of the other drugs being administered to the patients was evident. An ELISA also performed on the same samples overestimated the concentrations substantially, as indicated by a plot of the difference between the results for the two methods vs their mean. The favorable characteristics of the LC-MS2 assay, especially its sensitivity and specificity, will facilitate detailed pharmacokinetic studies of tacrolimus, particularly under circumstances in which metabolism is perturbed by either hepatic dysfunction or drug interactions.
Taylor
P J
PJ
Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane, Australia.
Jones
A
A
Balderson
G A
GA
Lynch
S V
SV
Norris
R L
RL
Pond
S M
SM
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D016031:Liver Transplantation; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D012680:Sensitivity and Specificity; D016559:Tacrolimus / Q000097:blood*; D013997:Time Factors
D007166:Immunosuppressive Agents; D016559:Tacrolimus