Degradation rates and products of fluticasone propionate in alkaline solutions

• Published in: Journal of pharmaceutical analysis 2017-10, Vol.7 (5), p.297-302
• Main Authors: Tokumura, Tadakazu, Yoshida, Naoko, Mori-Yasumoto, Kanami, Shirota, Osamu, Kurita, Takuro
• Format: Article
• Language: English
• Subjects: Adsorption; Alkaline solution; Aqueous solutions; Asthma; Biodegradation; Carboxylic acids; Chemical structure; Colon; Degradation products; Degradation rate; Fluticasone; Fluticasone propionate; High-performance liquid chromatography; Inflammatory bowel disease; Inflammatory bowel diseases; Intestinal microflora; Large intestine; Mass spectroscopy; Metabolism; Methanol; NMR; Nuclear magnetic resonance; Original; Pathogenesis; Pharmaceuticals; Pharmacology; products; Chemical; propionate; Degradation; Propionic acid; rate; Degradation; Sodium hydroxide; solution; structure; Alkaline
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2017.03.010

The apparent degradation rate constant of fluticasone propionate (FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169 ± 0.003 h?1, and four degradation products (products 1-4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH3CN=1:1 were 0.472 ± 0.013 h?1 and 0.154 ± 0.000 h?1 (n=3), respectively. The chemical structures of products 1-4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance (NMR) and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH3CN=1:1 was found to be product 2 based on 1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.