Mechanistic analysis on the photochemistry of the anti-inflammatory drug etoricoxib in aqueous solution. Cytotoxicity of photoproducts

Abstract

Photophysical and photochemical properties of the non-steroidal anti-inflammatory drug Etoricoxib was analyzing in aqueous media at different pH values. The mechanistic and kinetic aspects of the photodegradation processes involved, induced by UV irradiation of the drug were also investigated, as well as the generation of reactive oxygen species and transient excited species by the anti-inflammatory. Moreover, due to the fact that the photoproducts can be either less or more toxic than the parent pharmaceutical, the possible cytotoxic effects of etoricoxib and its photoproducts were analyzed in vitro on the Vero cell line. Etoricoxib undergoes pH-dependent photoinduced degradation processes when irradiated with UV light at 233 nm and 285 nm. The greater the degree of protonation, the greater the rate and quantum yield of photodegradation. The use of a variety of stationary and time-resolved techniques allowed us to propose a photodegradation mechanism for the anti-inflammatory. The main pathway involves the generation of an excited singlet state by UV light absorption that allows the formation of two isomeric photoproducts resulting from the photocyclization reaction of the excited etoricoxib. Likewise, the triplet excited state of the drug was detected and the spectrum of this transient species and its quantum yield are reported here for the first time. The triplet state could react with molecular oxygen and generate the reactive specie OH[rad] that lead to the photodegradation of the drug. On the other hand, it was possible to demonstrate that the products of the photocyclization can generated O2(1Δg) and be susceptible to photooxidation mediated by this species. By last, the in vitro cytotoxic test on Vero cell line (Neutral Red and MTT assay) revealed that the photoproducts can alter the viability of the cell by affecting de mitochondrial respiration processes.