Evaluation of photostability of azelnidipine tablets and structure determination of its photoproducts

• Published in: Journal of pharmaceutical and biomedical analysis 2023-09, Vol.233, p.115471-115471, Article 115471
• Main Authors: Kawabata, Kohei, Sakaue, Momoko, Akimoto, Shiori, Miyara, Masatsugu, Kotake, Yaichiro, Nishi, Hiroyuki
• Format: Article
• Language: English
• Subjects: Azelnidipine; Benzophenone; Chromatography, High Pressure Liquid - methods; Dihydropyridines; ESI-LC/MS/MS; Photodegradation; Photolysis; Photoproduct; Spectrometry, Mass, Electrospray Ionization - methods; Tablets
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2023.115471

Photo-exposure has a crucial effect on the natures of photosensitive pharmaceuticals in addition to their contents in medicines through the photodegradation. Generated photoproducts might be more bioactive and contribute to the expression of adverse side effects. This study aimed to clarify the photochemical behavior of medicines of azelnidipine, which is a member of dihydropyridine antihypertensive drugs, by the evaluation of its photostability and the determination of chemical structures of generated photoproducts. Calblock® tablets and its altered forms (powders and suspensions) were UV-irradiated by a black light. Residual amounts of active pharmaceutical ingredients (APIs) were monitored by high-performance liquid chromatography. The chemical structures of two photoproducts were determined by electrospray ionization tandem mass spectrometry. API of Calblock® tablets was photodegraded with the generation of several photoproducts. Its photodegradability was more significant when Calblock® tablets were crushed or suspended. Structural determination revealed that two photoproducts were benzophenone and a pyridine derivative. It was speculated that these photoproducts were generated by the elimination of diphenyl methylene radical and additional chemical reaction including oxidation and hydrolysis. Azelnidipine was photosensitive and its photodegradation in Calblock® tablets was promoted by the change of the dosage form. This difference might be derived from the light emission efficiency. This study suggests that API contents of Calblock® tablets might decrease when tablets or its altered forms are exposed to sunlight irradiation with the generation of benzophenone, which is a toxicological potent. •Photochemical behaviors of azelnidipine medicine and its altered forms are evaluated.•Azelnidipine in powders and suspensions are photodegraded by UV irradiation.•Main photoproduct of azelnidipine is benzophenone.•Another photoproduct of azelnidipine is a pyridine derivative.•Benzophenone is generated by the elimination of a diphenyl methylene moiety.