High-performance liquid chromatographic method for therapeutic drug monitoring of cyclosporine A and its two metabolites in renal transplant patients.
A novel fast HPLC method was developed for the determination of cyclosporine A (CyA) and its two metabolites M17 (AM1) and M21 (AM4N) in blood. Whole blood was precipitated with zinc sulphate, extracted with diethyl ether, evaporated, dissolved in aqueous methanol and partitioned twice with n-hexane. Chromatography was carried out using a microbore RP-column under isocratic elution with acetonitrile-methanol-water (200:80:140, v/v/v) at 70 degrees C and a detector set at 205 nm. Linearity for all three compounds was tested in the range of 1-1000 ng/ml. Recovery was 97-109%, and a coefficient of variation was 1.6-8.8% depending on the particular compound and its concentration. The method was used for a group of renal transplant patients having an inadequate response to CyA therapy in order to evaluate the possible role of CyA and its metabolites on the occurrence of hypertension and other toxicological events.
Brozmanová
H
H
Institute of Clinical Pharmacology, University Hospital and Medico-Social Faculty, University of Ostrava, Czech Republic. hana.brozmanova@fnspo.cz
Grundmann
M
M
Safarcík
K
K
Jegorov
A
A
D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016572:Cyclosporine / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D016030:Kidney Transplantation; D011863:Radioimmunoassay
D007166:Immunosuppressive Agents; D016572:Cyclosporine