Degradation rates and products of fluticasone propionate in alkaline solutions  

作　　者：Tadakazu Tokumura Naoko Yoshida Kanami Mori-Yasumoto Osamu Shirota Takuro Kurita 

机构地区：[1]Laboratory of Pharmaceutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University [2]Department of Pharmaceutical Sciences, School of Pharmacy, International University of Health and Welfare [3]Laboratory of Pharmacognosy and Natural Products Chemistry, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University

出　　处：《Journal of Pharmaceutical Analysis》2017年第5期297-302,共6页药物分析学报（英文版）

摘　　要：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:CH_3CN=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:CH_3CN=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.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:CH_3CN=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:CH_3CN=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.

关 键 词：FLUTICASONE PROPIONATE DEGRADATION RATE DEGRADATION PRODUCTS Chemical structure ALKALINE solution 

分 类 号：R914[医药卫生—药物化学]