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 analysis of tacrolimus and sirolimus in human blood by high-performance liquid chromatography-electrospray tandem mass spectrometry. Blood samples (500 microL) were prepared by C18 solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring. The assay was linear for both compounds over the range 0.25-100 microg/L (r2 > 0.996, n = 7). At the limit of quantification (0.25 microg/L), for both sirolimus and tacrolimus, the interday imprecision was < 3% and the analytical recovery was between 97.0% and 102%, respectively. The interbatch and intrabatch coefficients of variation of the method for both analytes, at the three quality control concentrations (0.5, 20, and 80 microg/L), were < 16% and < 10%, respectively. The analytical recovery, at the three control concentrations, ranged from 99.2% to 104% of the nominal concentration. The mean absolute recovery (+/- standard deviation) of tacrolimus, sirolimus, and internal standard was 82 +/- 7%, 89 +/- 12%, and 77 +/- 8%, respectively (n = 12). In conclusion, the method presented can be used for simultaneous determination of tacrolimus and sirolimus and will aid in pharmacokinetic studies and therapeutic drug monitoring of these drugs. Furthermore, this method has economic benefits in the clinical setting where these drugs are coadministered.
Taylor
P J
PJ
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane QLD, Australia.
Salm
P
P
Lynch
S V
SV
Pillans
P I
PI
D002851:Chromatography, High Pressure Liquid / Q000592:standards; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000592:standards*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D013058:Mass Spectrometry / Q000592:standards; D016377:Organ Transplantation; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus