Visible light-mediated photodegradation of imidazoline drugs in the presence of Riboflavin: Possible undesired effects on imidazoline-based eye drops

•Oxymetazoline and xylometazoline interacts with the excite states of Riboflavin.•Oxymetazoline is more easily photo-degradable than xylometazoline against ROS.•Upon direct UV- irradiation oxymetazoline and xylometazoline generate O2(1Δg). The imidazoline-based ophthalmic drugs oxymetazoline and xylometazoline are widely used as ocular decongestants in pharmaceutical preparations. In this paper, the degradation of these drugs and the model compound 2-methyl-2-imidazoline, was studied in the presence of the vitamin B2 (Riboflavin) and visible light. The photogenerated Riboflavin electronically excited triplet state interacts with oxymetazoline and xylometazoline and as a result different free radicals and reactive oxygen species are produced. These species interact with the drugs in further steps, producing their degradation. Oxymetazoline is more easily photo-degradable than xylometazoline towards reactive oxygen species. Particularly, oxymetazoline reacts four orders of magnitude faster than xylometazoline with singlet oxygen. This fact is due to the presence of an OH-group in the benzene ring of oxymetazoline, increasing the oxidability of the drug. The degradation of xylometazoline by reactive oxygen species becomes more important as its concentration increases. This finding should warn against long-time treatments with xylometazoline. An eventual local accumulation of the drug may cause adverse effects in the ocular organ in the presence of Riboflavin. In parallel, the present results advise for a moderate precaution in relation to light exposure after topical application of the imidazoline derivatives oxymetazoline and xylometazoline.