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 been developed for the analysis of L-691,121, a new antiarrhythmic agent, and its major metabolite, L-692,199, in plasma. Two RIAs using immunogens and radioligands prepared from different derivatives of L-691,121 were used in conjunction to determine both parent compound and metabolite 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 drug and metabolite displacement curves. The direct assay using 30 microliters of plasma is sensitive to 0.1 ng ml-1 and has sufficient precision, accuracy and specificity for the analysis of clinical samples.
Greber
T F
TF
Merck Research Laboratories, West Point, PA 19486.
Olah
T V
TV
Gilbert
J D
JD
Porras
A G
AG
Hichens
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood*; D000918:Antibody Specificity; D003429:Cross Reactions; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D010881:Piperidones / Q000097:blood*; D011817:Rabbits / Q000276:immunology; D011863:Radioimmunoassay; D013141:Spiro Compounds / Q000097:blood*
D000889:Anti-Arrhythmia Agents; D007202:Indicators and Reagents; D008024:Ligands; D010881:Piperidones; D013141:Spiro Compounds; C077569:L 691121; C089866:L 692199