title: Development and validation of a LC/MS/MS method for quantifying the next generation calcineurin inhibitor, voclosporin, in human whole blood.
abstract: 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.
authors.affiliation: Isotechnika Inc., 5120 - 75th Street, Edmonton, AB, Canada T6E 6W2.
authors.forename: Russell
authors.initials: R
authors.lastname: Handy
authors.forename: Dan
authors.initials: D
authors.lastname: Trepanier
authors.forename: Grace
authors.initials: G
authors.lastname: Scott
authors.forename: Robert
authors.initials: R
authors.lastname: Foster
authors.forename: Derrick
authors.initials: D
authors.lastname: Freitag
mesh_terms: 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*
chemical_list: D065095:Calcineurin Inhibitors; D016572:Cyclosporine