LC/ESI-MS allows simultaneous and specific quantification of SDZ RAD and cyclosporine, including groups of their metabolites in human blood

An analytic technique using liquid chromatography (LC) coupled with electro spray-mass spectrometry (ESI-MS) has been developed for the simultaneous de termination of the new immunosuppressant SDZ RAD (40-O-[2-hydroxy)ethylrapa mycin) and cyclosporine (Cs), including their metabolites in blood. With th e time-sparing, automated on-line extraction technique, the recovery of SDZ RAD averaged 95% and that of Cs, 94%. The calibration lines were linear fr om 0.5 to 100 mu g/L (r2 = 0.99) for SDZ RAD and from 10 to 1,000 mu g/L (r 2 = 0.99) for Cs. The method has been tested on blood samples from renal tr ansplant recipients taken between 1 and 5 hours after oral SDZ RAD and Cs a dministration. In blood, we found the following metabolites: Hydroxy-SDZ RA D, dihydroxy-SDZ RAD, demethyl-SDZ RAD, and the ring-opened form of SDZ RAD . The main metabolite of SDZ RAD in blood was hydroxy-SDZ RAD. This novel L C/ESI-MS technique provided an excellent method for simultaneous quantitati ve monitoring of SDZ RAD and Cs, including their relevant groups of metabol ites in patients treated simultaneously with these immunosuppressants.