Bernard Do
University of Paris-Sud, France
Title: Photo-reactivity assessment of perfusion drugs combining quantum chemical approach and experimental studies
Biography
Biography: Bernard Do
Abstract
The susceptibility of a drug substance or drug product to degrade upon light exposure is far from being an uncommon property. Actually, the number of drugs found to be photo-chemically unstable is steadily increasing and the European Pharmacopoeia recommends light protection for hundreds of medical drugs and a number of adjuvants. The evaluation of interactions between drugs and light accounts for a natural part of the research and development work for new medical products. This allows the formulations containing drugs susceptible to photoreactions to be marked and adequately stored. However, in some situations, the ideals are not always maintained. Indeed, it is well known that in-use conditions do not always coincide with the control or design spaces, within which, it has been shown that the drug is stable. In this context, liquid preparations are much more concerned than solid formulations of the corresponding drug substances, being usually far more photolabile. That's why elucidating photodegradation mechanisms of drug products can be of paramount importance in that this can help reckon whether special procedures or additives could be used to prevent any loss of drug potency and formation of photoproducts during their handling and administration. We present here an approach combining a computational method based upon the density functional theory (DFT) and experimental studies using liquid chromatography-multistage mass spectrometry (LC-MSn) to investigate the photodegradation behaviour of parenteral drugs through two case studies, tirofiban and raltitrexed. The results predicted by DFT were experimentally supported through the photoproducts identification. As their photoreactions were shown to mainly proceed through type I and type II photosensitization mechanisms, the possibility of adding quenchers to the formulation can be considered. The major contenders would be substances such as ascorbic acid, a-tocopherol, and BHT, which are capable of acting as free radical scavengers and weak singlet oxygen quenchers.