QUALITY ASSURANCE PROGRAM FOR CYCLOSPORINE-G (OG37-325)

Cyclosporine-G (CsG) (OG37-325) an analogue of cyclosporine-A (CsA) is presently undergoing clinical trials. As therapeutic monitoring of Cs G was an integral part of these evaluations, the performance of labora tories measuring the drug was assessed through an external quality ass urance program, which included all North American centers participatin g in the trials. The assays used by participating centers were high-pe rformance liquid chromatography (HPLC) (n = 3), radioimmunoassay (RIA) (n = 5), and fluorescence polarization immunoassay (FPIA) (n = 24). T he latter two assays, developed for measurement of CsA, were adapted f or measurement of CsG. The FPIA was the most precise, with the largest proportion of laboratories reporting coefficients of variation (CNs) of < 10%. RIA was the least accurate method, with similar to 74% of re sults differing by > 20% from target values. FPIA and RIA methods exhi bited mean recoveries of CsG of 112 and 129%, respectively. The rankin g of the specificity of the assays from measurement of parent drug was HPLC > RIA > FPIA. FPIA and RIA produced values that were, on average , similar to 60% higher than those reported by HPLC in pooled whole bl ood specimens obtained from renal transplant patients. It is recommend ed that if CsG is approved for routine clinical use, then assays devel oped specifically for measurement of the drug be used.