142780-68-5Relevant academic research and scientific papers
Autoxidation of drugs: Prediction of degradation impurities from results of reaction with radical chain initiators
Boccardi
, p. 431 - 435 (2007/10/02)
In the study of the degradation of drug substances by molecular oxygen, their specific reaction mechanisms must be taken into account. The rate- determining step is usually the reaction of the substrate with a radical chain initiator, which is often an unknown impurity. The reactivity and selectivity of autoxidation can be controlled better by using a radical chain initiator, such as AIBN, than by changing the temperature or the oxygen pressure. In this paper the products profiles of four pharmaceutical substances in a simple oxidation test with AIBN are compared with the results of long term natural stability tests or with already established stabilities.
Autoxidation of tetrazepam in tablets: Prediction of degradation impurities from the oxidative behavior in solution
Boccardi,Deleuze,Gachon,Palmisano,Vergnaud
, p. 183 - 185 (2007/10/02)
The major route of degradation of tetrazepam (1) is oxidation to 7-chloro- 5-(3-keto-cyclohexen-1-yl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (3) via the stable 7-chloro-5-(3-hydroperoxy-cyclohexen-1-yl)-1,3-dihydro-1- methyl-2H-1,4 benzodiazepin-2-one (2). Minor degradation products are 7- chloro-5-(1,2-epoxycyclohexan-1-yl)-1,3-dihydro-1-methyl-2H-1,4- benzodiazepin-2-one (5) and 7-chloro-1,3-dihydro-1-methyl-2H-1,4- benzodiazepin-2,5-dione (4), resulting from cleavage of the C-C bond between the cyclohexene ring and the benzodiazepine ring. After 48 h, AIBN (2,2'- azobis[2-methyl-propanenitrile]) in acetonitrile at 40 °C produced qualitatively the same impurities as those observed in the stability study of tablets of 1. Other stress tests (thermal stress at 80 °C, heavy metal oxidation, hydrogen peroxide, acid-catalyzed oxidation) caused qualitatively different profiles of degradation.
