A sensitive assay for the pharmacokinetic investigation of a rapidly hydrolyzing alkylating agent Lycurim (ritrosulfan; R-74; NSC-122 402).
Lycurim [1,4-di(2'-methanesulfonyloxyethylamino)-1,4-dideoxymesoerythri tol dimethane sulfonate] is rapidly hydrolyzed in aqueous media to inactive products according to a second-order reaction. The respective rate constants are: k1 = 9.82 X 10(-2) and k2 = 1.76 X 10(-2) mumol/ml/min. The concentrations of the parent compound and alkylating intermediate(s) were measured by chemical trapping with N,N-diethyldithiocarbamic acid (DDTC). The rate of this reaction is substantially higher: k1 = 2.61 X 10(-1) and K2 = 4.76 X 10(-2) mumol/ml/min. By using 35S-labeled DDTC, alkylating compounds in concentrations as low as 0.04 microgram/ml could be detected in spiked plasma samples. After intracavitary application of 60 mg Lycurim no alkylating activity could be demonstrated in the plasma of patients at any time point.
D000477:Alkylating Agents / Q000097:blood / Q000378:metabolism*; D004050:Ditiocarb / Q000378:metabolism; D004896:Erythritol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008722:Methods; D010996:Pleural Effusion / Q000378:metabolism
D000477:Alkylating Agents; D004050:Ditiocarb; D004896:Erythritol; C000288:ritrosulfan