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 electrospray-mass spectrometry (ESI-MS) has been developed for the simultaneous determination of the new immunosuppressant SDZ RAD (40-O-[2-hydroxy)ethylrapamycin) and cyclosporine (Cs), including their metabolites in blood. With the time-sparing, automated on-line extraction technique, the recovery of SDZ RAD averaged 95% and that of Cs, 94%. The calibration lines were linear from 0.5 to 100 microg/L (r2 = 0.99) for SDZ RAD and from 10 to 1,000 microg/L (r2 = 0.99) for Cs. The method has been tested on blood samples from renal transplant recipients taken between 1 and 5 hours after oral SDZ RAD and Cs administration. In blood, we found the following metabolites: Hydroxy-SDZ RAD, 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 LC/ESI-MS technique provided an excellent method for simultaneous quantitative monitoring of SDZ RAD and Cs, including their relevant groups of metabolites in patients treated simultaneously with these immunosuppressants.
Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Germany.
G I
GI
Kirchner
C
C
Vidal
M
M
Winkler
L
L
Mueller
W
W
Jacobsen
A
A
Franzke
K F
KF
Sewing
D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood* / Q000378:metabolism; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000378:metabolism; D013058:Mass Spectrometry; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus