DETOXIFICATION OF AN ALKYLATING DRUG, N,N-BIS(2-CHLOROETHYL)-P-AMINOPHENYLBUTYRIC ACID (CHLORAMBUCIL), IN HUMAN GASTRIC-JUICE AND SALIVA

N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid(chlorambucil, 1) is a n orally administered drug widely used in the chemotherapy of chronic lymphocytic leukemia. It is converted in gastric juice into three stab le metabolites, which were characterized as N,N-bis(2-hydroxyethyl)-p- aminophenylbutyric acid (4), ethyl)-N-[2-(thiocyano)ethyl]-p-aminophen ylbutyric acid (5), and N,N-bis[2-(thiocyano)ethyl]-p-aminophenylbutyr ic acid (6). 4 is the product of chloroambucil hydrolysis, while 5 and 6 are results of the reaction of 1 with saliva-derived thiocyanate io n. The destabilizing effect of low gastric oxonium ion concentration o n 1 is also demonstrated.