J. Hovinen et al., DETOXIFICATION OF AN ALKYLATING DRUG, N,N-BIS(2-CHLOROETHYL)-P-AMINOPHENYLBUTYRIC ACID (CHLORAMBUCIL), IN HUMAN GASTRIC-JUICE AND SALIVA, Chemical research in toxicology, 11(2), 1998, pp. 91-93
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.