title: Rapid, sensitive high-performance liquid chromatographic method for the determination of cyclosporin A and its metabolites M1, M17 and M21.
abstract: Cyclosporin A (CyA) and its metabolites seem to have nephro-, hepato- and neurotoxic side effects. Immunosuppressive therapy is a narrow path between the risk of rejection by underimmunosuppression and toxic organ damage by overdosage. Thus CyA dosage must be calculated to avoid the risks of organ rejection through underdosage and toxic organ damage through overdosage or accumulation of metabolites. In routine monitoring of CyA therapy, it can be important to measure not only the parent drug but also the metabolites. We describe a rapid and isocratic high-performance liquid chromatographic method for measurement of CyA and its metabolites M1, M17 and M21 in whole blood. CyA was detected by ultraviolet absorption at 212 nm with a CN analytical column maintained at 50 degrees C and recycling of hexane-isopropanol as mobile phase for improved long-term column stability and efficiency. The minimum detectable concentration of CyA and the three metabolites was 10 ng/ml blood. Our modified HPLC method for the determination of CyA and its metabolites is a simple (isocratic), rapid (the retention times were 7.1 min for CYD, internal standard, 8.9 min for CyA, 11.0 min for M21, 12.9 min for M17 and 16.3 min for M1) and economical method suitable for measuring the concentration of the major metabolite, M17, and for routine monitoring of CyA-treated patients.
authors.affiliation: Department of Laboratory Medicine, University of Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Khoschsorur
authors.forename: H J
authors.initials: HJ
authors.lastname: Semmelrock
authors.forename: S
authors.initials: S
authors.lastname: Rödl
authors.forename: T
authors.initials: T
authors.lastname: Auer
authors.forename: W
authors.initials: W
authors.lastname: Petek
authors.forename: F
authors.initials: F
authors.lastname: Iberer
authors.forename: K H
authors.initials: KH
authors.lastname: Tscheliessnigg
mesh_terms: D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood*; D003524:Cyclosporins / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D015203:Reproducibility of Results
chemical_list: D003524:Cyclosporins; D007166:Immunosuppressive Agents; C106029:M1 cyclosporin metabolite; D016572:Cyclosporine; C059204:cyclosporine metabolite M21; C051527:cyclosporine metabolite M17