Measurement of the class III antidysrhythmic drug, UK-68,798, in plasma by radioimmunoassay.
A sensitive radioimmunoassay (RIA) for the specific determination of 1-(4-methanesulphonamidophenoxy)-2-[N-(4-methanesulphonamido -phenethyl)-N- methylamino]ethane (UK-68,798), a novel class III antidysrhythmic agent, in human plasma is described. Specific antisera were raised in sheep using desmesyl-UK-68,798-succinate-ovalbumin conjugate as the antigenic hapten carrier protein. The antisera produced exhibited high specificity for UK-68,798 compared with known metabolites from animals, other antidysrhythmic agents and co-administered drugs. Good correlation was found in a comparison of the RIA method with a high-performance liquid chromatography (HPLC) method (r = 0.997) and a 10-fold lower limit of determination was observed for the RIA method compared with the HPLC method (0.05 and 0.5 ng ml-1, respectively). The RIA method was applied to the analysis of UK-68,798 in plasma obtained from human volunteers receiving the compound.
Walker
D K
DK
Department of Drug Metabolism, Pfizer Central Research, Kent, UK.
Aherne
G W
GW
Arrowsmith
J E
JE
Cross
P E
PE
Kaye
B
B
Smith
D A
DA
Stopher
D A
DA
Wild
W
W
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood*; D000918:Antibody Specificity; D001322:Autoanalysis; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006241:Haptens / Q000032:analysis / Q000138:chemical synthesis; D010627:Phenethylamines / Q000097:blood* / Q000138:chemical synthesis / Q000276:immunology; D011863:Radioimmunoassay; D051381:Rats; D012756:Sheep / Q000276:immunology; D013449:Sulfonamides / Q000097:blood* / Q000138:chemical synthesis / Q000276:immunology
D000889:Anti-Arrhythmia Agents; D006241:Haptens; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide