Simultaneous quantification of tacrolimus and sirolimus, in human blood, by high-performance liquid chromatography - Tandem mass spectrometry

In this paper the authors present a validated method for the simultaneous a nalysis of tacrolimus and sirolimus in human blood by high-performance liqu id chromatography-electrospray tandem mass spectrometry. Blond samples (500 mu L) were prepared by C-18 solid-phase extraction. Mass spectrometric det ection was by selected reaction monitoring. The assay was linear far both c ompounds over the range 0.25-100 mu g/L (r(2) > 0.996, n = 7). At the limit of quantification (0.25 mu g/L), for both sirolimus and tacrolimus, the in terday imprecision was <3% and the analytical recovery was between 97.0% an d 102%, respectively, The interbatch and intrabatch coefficients of variati on of the method for both analytes, at the three quality control concentrat ions (0.5, 20, and 80 mu g/L). were <16% and <10%, respectively. The analyt ical recovery, at the three control concentrations, ranged from 99.2% to 10 4% of the nominal concentration. The mean absolute recovery (+/-standard de viation) of tacrolimus. sirolimus. and internal standard was 82 +/- 7%, 89 +/- 12%, and 77 +/- 8%, respectively (n = 12). In conclusion, the method pr esented can be used for simultaneous determination of tacrolimus and siroli mus and will aid in pharmacokinetic studies and therapeutic drug monitoring of these drugs. Furthermore, this method has economic benefits in the clin ical setting where these drugs are coadministered.