Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor
Simvastatin (SV) is a semisynthetic derivative of lovastatin (LV), which is biosynthetically produced from the fungus <i>Aspergillus terreus</i> and has a high log <i>p</i> value (log <i>p</i> = 4.39)and thus high hepatic extraction and high efficacy in controllin...
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MDPI AG
2022-11-01
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| Series: | Separations |
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| Online Access: | https://www.mdpi.com/2297-8739/9/12/400 |
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| author | Wencui Yin Reem I. Alwabli Mohamed W. Attwa A. F. M. Motiur Rahman Adnan A. Kadi |
| author_facet | Wencui Yin Reem I. Alwabli Mohamed W. Attwa A. F. M. Motiur Rahman Adnan A. Kadi |
| author_sort | Wencui Yin |
| collection | DOAJ |
| description | Simvastatin (SV) is a semisynthetic derivative of lovastatin (LV), which is biosynthetically produced from the fungus <i>Aspergillus terreus</i> and has a high log <i>p</i> value (log <i>p</i> = 4.39)and thus high hepatic extraction and high efficacy in controlling cholesterol synthesis. The current study was undertaken to investigate the metabolic profile of SV using various mass spectrometry (MS) platforms. Metabolic profiling was studied in in vitro models, rat liver microsomes (RLMs), and isolated perfused rat liver hepatocytes (RLHs) using both ion trap and triple quadruple LC–MS/MS systems. A total of 29 metabolites were identified. Among them, three types of SV-related phase-I metabolites, namely exomethylene simvastatin acid (exomethylene SVA), monohydroxy SVA, and dihydrodiol SVA, were identified as new in RLMs. No phase-II metabolites were identified while incubating with RLHs. |
| first_indexed | 2024-03-09T15:51:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2297-8739 |
| language | English |
| last_indexed | 2024-03-09T15:51:51Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
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| spelling | doaj.art-b2201249de404b73882289181d5079542023-11-24T17:59:27ZengMDPI AGSeparations2297-87392022-11-0191240010.3390/separations9120400Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase InhibitorWencui Yin0Reem I. Alwabli1Mohamed W. Attwa2A. F. M. Motiur Rahman3Adnan A. Kadi4Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaSimvastatin (SV) is a semisynthetic derivative of lovastatin (LV), which is biosynthetically produced from the fungus <i>Aspergillus terreus</i> and has a high log <i>p</i> value (log <i>p</i> = 4.39)and thus high hepatic extraction and high efficacy in controlling cholesterol synthesis. The current study was undertaken to investigate the metabolic profile of SV using various mass spectrometry (MS) platforms. Metabolic profiling was studied in in vitro models, rat liver microsomes (RLMs), and isolated perfused rat liver hepatocytes (RLHs) using both ion trap and triple quadruple LC–MS/MS systems. A total of 29 metabolites were identified. Among them, three types of SV-related phase-I metabolites, namely exomethylene simvastatin acid (exomethylene SVA), monohydroxy SVA, and dihydrodiol SVA, were identified as new in RLMs. No phase-II metabolites were identified while incubating with RLHs.https://www.mdpi.com/2297-8739/9/12/400simvastatinSVSVARLMsRLHs |
| spellingShingle | Wencui Yin Reem I. Alwabli Mohamed W. Attwa A. F. M. Motiur Rahman Adnan A. Kadi Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor Separations simvastatin SV SVA RLMs RLHs |
| title | Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor |
| title_full | Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor |
| title_fullStr | Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor |
| title_full_unstemmed | Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor |
| title_short | Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor |
| title_sort | simvastatin in vitro metabolic profiling of a potent competitive hmg coa reductase inhibitor |
| topic | simvastatin SV SVA RLMs RLHs |
| url | https://www.mdpi.com/2297-8739/9/12/400 |
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