Quantitation of cyclosporin A in whole blood by liquid chromatography/stable isotope dilution electrospray ionization mass spectrometry.
Therapy with cyclosporin A (CsA) for immunosuppression after organ transplantation requires monitoring of its levels in blood owing to the narrow therapeutic index of the drug and to the high inter-individual variability of the drug absorption and metabolism. We describe the preparation of CsA labelled with stable isotopes ((13)C and (2)H) with an isotopic enrichment of about 99% using labelled glucose and its use as internal standard for quantification of CsA blood levels by isotope dilution/electrospray ionization mass spectrometry. The method was found to be linear in the tested range (1-1000 ng) with and without the matrix. The accuracy of the bracketting calibration curves prepared using 100 ng ml(-1) labelled CsA was within +/-1.7% (bias). The results confirmed the usefulness of the procedure as a reference method for the external quality assessment of the field methods for the evaluation of CsA blood concentration, the imprecision (relative standard deviation) and accuracy (bias) being <2%.
Magni
F
F
Laboratorio di Spettrometria di Massa, IRCCS San Raffaele, 20132 Milan, Italy. magni.fulvio@hsr.it
Pereira
S
S
Leoni
M
M
Grisenti
G
G
Galli Kienle
M
M
D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D016572:Cyclosporine / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization
D007166:Immunosuppressive Agents; D012996:Solutions; D016572:Cyclosporine