Improved liquid-chromatographic determination of cyclosporine and its metabolites in blood.

We describe a liquid-chromatographic assay for cyclosporine (CyA) and four of its metabolites in blood. The method is sensitive and specific for this drug and its metabolites. The use of flow programming shortens total chromatographic run time to 30 min, resulting in acceptable separation of metabolites at a lower flow rate and yielding narrower peaks for CyA and the internal standard at the higher flow rate. CyA and metabolites Met 17 and Met 1 were measured in seven heart transplant patients who were undergoing chronic therapy with CyA in oral doses ranging from 3 to 13 mg/kg body wt per day. For the individual patients, the mean trough concentrations in blood of CyA, Met 17, and Met 1 ranged from 111 to 221, 159 to 334, and 36 to 90 micrograms/L, respectively. Met 8 and Met 21 were not observed in any of these patients' blood specimens.