Photolysis of cocaine, morphine, D9-tetrahydrocannabinol and EDDP in water solution.

In the frame of an ongoing project aimed at understanding the mechanisms of photodegradation and characterizing the phototoxicological profile of drugs and illicit drugs and their photosensitizing role in the biological systems [1-4], the photostability towards UVA and UVB light of cocaine, 9-tetrahydrocannabinol (THC), morphine and EDDP in water solution has been studied. The extent of photolysis and the kind of photoproducts formed have been studied by UV-Vis spectrophotometric analysis, HPLC chromatography, HRMS, and HRMS/MS analysis for accurate mass measurement of small molecules. HPLC analysis allowed us to calculate the yield of photolysis; in particular, Cocaine showed photolysis under high UV light doses, forming demethylated and hydroxylated photoproducts, and the inactive metabolite ecgonyne methyl ester, as already reported in the literature under solar irradiation and photocatalytic processes [5]. Morphine proved also to be unstable under UVB light and, in lower extent, under UVA. It forms various photoproducts, some of them corresponding to oxidation products or deriving from the addition of water to the 7,8 double bond. Also the absorption spectrum of EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), the main inactive metabolite of methadone, changes under increasing light doses, with the appearance of a new band between 300 and 350 nm. Under both UVA and UVB irradiation, it forms various degradation products, one of them dehydrogenated and another one losing also the ethyl group. For another one we suppose the loss of one of the two aromatic rings. THC also showed photolability under both UVA and UVB light. Its photodegradation products are still under investigation. Since the photo excited drugs could photo react directly with biological substrates, produce free radicals and reactive oxygen species , or even give rise to toxic photoproducts, particularly oxidation compounds, the phototoxicological profile of illicit drugs and their photoproducts covers particular importance in the study of the toxicity/ phototoxicity of compounds in the aquatic environment.