Degradation rates and products of fluticasone propionate in alkaline solutions
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...
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Elsevier
2017-10-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177917300230 |
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| author | Tadakazu Tokumura Naoko Yoshida Kanami Mori-Yasumoto Osamu Shirota Takuro Kurita |
| author_facet | Tadakazu Tokumura Naoko Yoshida Kanami Mori-Yasumoto Osamu Shirota Takuro Kurita |
| author_sort | Tadakazu Tokumura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T18:10:39Z |
| format | Article |
| id | doaj.art-9f2a677570324783a7ad759d6210babc |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-12-13T18:10:39Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-9f2a677570324783a7ad759d6210babc2022-12-21T23:35:58ZengElsevierJournal of Pharmaceutical Analysis2095-17792017-10-017529730210.1016/j.jpha.2017.03.010Degradation rates and products of fluticasone propionate in alkaline solutionsTadakazu Tokumura0Naoko Yoshida1Kanami Mori-Yasumoto2Osamu Shirota3Takuro Kurita4Laboratory of Pharmaceutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki, Kagawa 769-2193, JapanDepartment of Pharmaceutical Sciences, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, JapanLaboratory of Pharmacognosy and Natural Products Chemistry, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki, Kagawa 769-2193, JapanLaboratory of Pharmacognosy and Natural Products Chemistry, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki, Kagawa 769-2193, JapanLaboratory of Pharmaceutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki, Kagawa 769-2193, JapanThe 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.http://www.sciencedirect.com/science/article/pii/S2095177917300230Fluticasone propionateDegradation rateDegradation productsChemical structureAlkaline solution |
| spellingShingle | Tadakazu Tokumura Naoko Yoshida Kanami Mori-Yasumoto Osamu Shirota Takuro Kurita Degradation rates and products of fluticasone propionate in alkaline solutions Journal of Pharmaceutical Analysis Fluticasone propionate Degradation rate Degradation products Chemical structure Alkaline solution |
| title | Degradation rates and products of fluticasone propionate in alkaline solutions |
| title_full | Degradation rates and products of fluticasone propionate in alkaline solutions |
| title_fullStr | Degradation rates and products of fluticasone propionate in alkaline solutions |
| title_full_unstemmed | Degradation rates and products of fluticasone propionate in alkaline solutions |
| title_short | Degradation rates and products of fluticasone propionate in alkaline solutions |
| title_sort | degradation rates and products of fluticasone propionate in alkaline solutions |
| topic | Fluticasone propionate Degradation rate Degradation products Chemical structure Alkaline solution |
| url | http://www.sciencedirect.com/science/article/pii/S2095177917300230 |
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