LC-UV and LC-MS evaluation of stress degradation behaviour of avizafone

It has been known for many years that benzodiazepine compounds effectively antagonize seizures induced by organophosphorous nerve agents. In the event of poisoning, a combination of three drugs is commonly used: an anticholinergic drug (e.g. atropine), an oxime used as cholinesterase reactivator (e.g. pralidoxime or HI-6) and an anticonvulsant (i.e. benzodiazepine). Most of anticholinergics and oximes are freely soluble in water, whereas many benzodiazepines are not. However, a water-soluble prodrug form of diazepam, avizafone, has been adopted by French armed forces for the immediate treatment of nerve agent seizure. The degradation behaviour of this new drug was investigated under different stress degradation conditions (hydrolytic, oxidative, photolytic and thermal) as recommended by International Conference on Harmonization. Successful separation of the active pharmaceutical ingredient from decomposition products formed under stress conditions was achieved using liquid chromatography. The method was validated with respect to specificity, linearity, precision and accuracy.