Phototransformation patterns of the antiplatelet drug tirofiban in aqueous solution, relevant to drug delivery and storage

Abstract

Tirofiban is a synthetic, nonpeptidic fibrinogen receptor antagonist used as an antiplatelet drug for intravenous delivery. As the active pharmaceutical ingredient may undergo light exposure during manufacturing, storage and/or delivery, there is a need to acquire an extensive knowledge of its major photochemical-degradation pathways. Thus, photochemical-degradation of tirofiban under simulated light irradiation in aqueous solution and in the absence of photosensitizers or photocatalysts, has been investigated in terms of mechanisms. The structural characterization of the photochemical products was carried out with using performance liquid chromatography-multistage high-resolution mass spectrometry along with on-line hydrogen/deuterium exchange. The identification of the twelve detected photochemical products suggested that the photo-transformation of tirofiban occurred via multiple reaction pathways, initiated either by electron or hydrogen atom transfer. These included the photo-oxidation of the piperidine moiety without impacting the secondary amine, the hydroxylation of the methylene group activated by the aromatic ring, the oxidation of the alkyl-sulfonamide group and also the decarboxylative oxidation of the molecule. Hydroxylated compounds, geminal and vicinal-diol compounds, were highlighted suggesting that most of the photoproducts are more hydrophilic than the drug. Understanding the main photo-degradation routes is a good basis to work out efficient measures so as to mitigate or avoid tirofiban instability.