Therapeutic monitoring of cyclosporine: impact of a change in standards on 125I-monoclonal RIA performance in comparison with liquid chromatography.

This study examines the measurement of cyclosporine (CsA) by 125I-monoclonal RIA, and describes the impact of the recent change in the standard curve provided. CsA concentrations in serum and whole-blood control samples measured by 125I-RIA were initially 8-18% higher than those by HPLC. During the first two months of 1989, a significant and sustained deviation in the 125I-RIA produced results that exceeded the HPLC results by 21-28% (P less than 0.001). Introduction of the new standard curve in March 1989 returned the concentration of the whole-blood controls to the previous range (11-12% above HPLC, P less than 0.001). Measurement of clinical samples from heart, liver, and bone-marrow graft recipients by 125I-RIA by both old and new kit standards produced a close linear correlation (y = 0.89 x - 19.02; r = 0.99; n = 75, range = 40-850 micrograms/L), with use of the new standards yielding results 82 (SD 8)% of those with the preceding assay. However, even with the new standard curve, CsA concentrations by 125I-RIA in the clinical samples exceeded those by HPLC by a factor of 1.37 (SD 0.18) to 1.52 (SD 0.19). Segregation for transplant type did not affect the RIA/HPLC ratio. The results suggest cross-reactivity of the 125I-RIA with material present in vivo.