DETERMINATION OF L-691,121, A NEW CLASS-III ANTIARRHYTHMIC, AND ITS PRINCIPAL METABOLITE IN PLASMA BY DIFFERENTIAL RADIOIMMUNOASSAY

A sensitive and specific method based on radioimmunoassay (RIA) has be en developed for the analysis of L-698,121, a new antiarrhythmic agent , and its major metabolite, L-692,199, in plasma. Two RIAs using immun ogens and radioligands prepared from different derivatives of L-691,12 1 were used in conjunction to determine both parent compound and metab olite concentrations by solving simultaneous equations, since neither assay alone was adequately specific. Variable cross-reactivity factors were incorporated into the calculations to correct for non-parallel d rug and metabolite displacement curves. The direct assay using 30 mul of plasma is sensitive to 0.1 ng ml-1 and has sufficient precision, ac curacy and specificity for the analysis of clinical samples.