Development of a radioimmunoassay for determination of the dopamine D-4 receptor antagonist, L-745,870, in human plasma cross validated with LC-MS/MS

L-745,870, a D-4 receptor antagonist, is an antipsychotic drug candidate. A sensitive and specific method based on radioimmunoassay (RIA) has been dev eloped for the determination of this drug in plasma. The immunogen was prep ared by coupling the N-hydroxysuccinimide ester of a carboxylic acid deriva tive (L-760,711) of L-745,870 to bovine serum albumin. Antiserum was obtain ed from rabbits immunized over a 6-month period. The radioligand was prepar ed by reacting this N-hydroxysuccinimide ester with [I-125]iodotyrosine, Th e method was deemed specific as no immunoreactive material other than the p arent drug was detected in plasma. This assay uses 20 mu L of plasma direct ly and is sensitive to 0.25 ng/mL with satisfactory accuracy and precision, The specificity of the RIA was confirmed following cross validation with a LC-MS/MS based analytical method using results obtained from the analysis of patients' samples.