NEW UNLABELLED AND RADIOACTIVE LABELLED DERIVATIVES OF BUTYLAMINO PROPIOPHENONE,THEIR PREPARATION,IMMUNOGENS OBTAINED FROM THE UNLABELLED DERIVATIVES AND A PROCESS FOR IMMUNOGEN PREPARATION ANTISERA RAISED USING THE IMMUNOGENS AND A METHOD FOR RAISING ANTISERA,A RADIOIMMUNOASSAY METHOD AND A TEST KIT FOR USE IN THE ASSAY METHOD

摘要

A radioimmunoassay procedure has been discovered for bupropion [(+/-)-2-t-butylamino-3-chloropropiophenone], an antidepressant compound, in biological fluids. Novel compounds of formula IMAGE wherein either R2 is oxygen and R1 is (CH2)n-0-(CO)m-(CH2)p-COOH where n is an integer from 0 to 5, m is 0 or 1, and p is an integer from 1 to 4; or R1 is hydrogen and R2 is N-0-(CH2)q-COOH where q is an integer from 1 to 3, and novel methods of making them and novel intermediates useful therein are disclosed. Novel immunogens for raising bupropion specific antisera, and novel methods of making them are disclosed comprising conjugates of the novel compounds and suitable carrier material. The drug is added to the antisera together with novel radiolabeled competitor of formula IMAGE wherein R' is a suitable radioisotope as described above and R3 is hydrogen, R4 is Cl, and R5 is oxygen, or R' is hydrogen and either (a) R3 is H and R4 is Cl and R5 is NO(CH2)qCO-X where q is as defined for formula I and X is a group having formula III IMAGE III wherein R6 is a suitable radioisotope as described above, R7 is hydroxyl, and s is an integer from 1 to 4; (b) R4 is Cl, R5 is oxygen, and R3 is (CH2)n-0-(CO)m-(CH2)p-CO-X where n, m, and p are as defined for formula I and X is as defined above; or (c) R3 is hydroxy, R5 is oxygen and R4 is a suitable radioisotope as defined above. The measure of radioactivity of the antisera bound radiolabeled competitor provides a measure of the amount of drug in the assayed biological fluid sample. A standard curve can be constructed from which the amount of drug in the assay sample can be interpolated. A kit is disclosed for practicing the radioimmunoassay.