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.
Kirchner
G I
GI
Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Germany.
Vidal
C
C
Winkler
M
M
Mueller
L
L
Jacobsen
W
W
Franzke
A
A
Sewing
K F
KF
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