Cost-effective synthesis and pharmaceutical-grade purification of phenytoin anticonvulsant for use in economically developing countries

Phenytoin is listed by the World Health Organization as an Essential Medicine that is one of the most cost-effective anti-epileptic (AED) treatments available. However, availability of the drug to pharmacies in developing countries is limited. 85% of those affected with epilepsy live without treatment. Low commercial production, political instabilities, and/or financial barriers prevent this anti-epileptic availability. A more efficient and cost-effective method for supplying phenytoin to local clinics and medical personnel could alleviate some of these barriers. The goal of this project was to create a benchtop method for the small-scale synthesis and purification of phenytoin using base-catalyzed addition of urea to benzil followed by pinacol rearrangement and recrystallization, emphasizing simple lab procedure found in the most basic of pharmacy laboratories. Using the International Pharmacopoeia guidelines for pharmaceutical purity, we achieved over 98% purity. Verification of pharmaceutical grade purity was achieved by liquid chromatography-mass spectrometry (LCMS).