Development and validation of a LC/MS/MS method for quantifying the next generation calcineurin inhibitor, voclosporin, in human whole blood.
A rapid, accurate, and reproducible liquid chromatography electrospray tandem mass spectrometry (LC/ESI-MS/MS) method was developed and validated for the therapeutic drug monitoring of voclosporin in human whole blood. Sample aliquots of 100muL were processed utilizing a protein precipitation procedure that contained a mixture of methanol, 0.2M ZnSO(4), and deuterated voclosporin internal standard. Supernatant was injected onto a Zorbax SB-C8, 2.1x12.5mm column (at 60 degrees C), and washed with water-acetonitrile, supplemented with 0.02% glacial acetic acid and 0.02mM sodium acetate, to remove poorly retained components. After washing, water-MeOH (with 0.02% glacial acetic acid and 0.02mM sodium acetate) was used to elute the voclosporin and internal standard to the Applied Biosystems/MDS-Sciex API3000 mass spectrometer for detection in multiple reaction monitoring. Analytical performance was assessed in the range of 1-200ng/ml in whole blood. This method has been used to quantify concentrations of voclosporin in whole blood from healthy volunteers participating in a pharmacokinetic study.
Handy
Russell
R
Isotechnika Inc., 5120 - 75th Street, Edmonton, AB, Canada T6E 6W2.
Trepanier
Dan
D
Scott
Grace
G
Foster
Robert
R
Freitag
Derrick
D
D065095:Calcineurin Inhibitors; D002853:Chromatography, Liquid / Q000379:methods*; D016572:Cyclosporine / Q000097:blood* / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
D065095:Calcineurin Inhibitors; D016572:Cyclosporine