Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry Method
Enavogliflozin, a sodium–glucose cotransporter 2 inhibitor, was approved in 2022 by the Korean Ministry of Food and Drug Safety as a therapeutic agent for type 2 diabetes mellitus and has been investigated for expanded therapeutic efficacy in diabetic retinopathy and cardioprotection. In this study,...
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2025-01-01
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| author | Minyeong Pang Jihoon Lee Min-Koo Choi Im-Sook Song |
| author_facet | Minyeong Pang Jihoon Lee Min-Koo Choi Im-Sook Song |
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| description | Enavogliflozin, a sodium–glucose cotransporter 2 inhibitor, was approved in 2022 by the Korean Ministry of Food and Drug Safety as a therapeutic agent for type 2 diabetes mellitus and has been investigated for expanded therapeutic efficacy in diabetic retinopathy and cardioprotection. In this study, we developed and validated an analytical method to precisely detect enavogliflozin in mouse plasma, employing liquid–liquid extraction combined with liquid chromatography–tandem mass spectrometry. Overall, the analytical method, covering a range of 5–3000 ng/mL, is reliable for investigating the time-concentration profiles of enavogliflozin, demonstrating acceptable accuracy, precision, extraction recovery, and minimal matrix effects without stability concerns as evidenced by assessments of post-treatment stability, freeze–thaw stability, and short-term stability of enavogliflozin. Pharmacokinetic profiles and all pharmacokinetic parameters of enavogliflozin in mice did not differ between fed and fasted states after oral administration of enavogliflozin (1 mg/kg). Additionally, no differences in the pharmacokinetic profiles of enavogliflozin were observed among single, 7-day repeated, and 14-day repeated oral administrations at 1 mg/kg. In the tissue distribution study, enavogliflozin showed the highest distribution in the kidneys, followed by the large intestine, stomach, small intestine, liver, heart, lungs, spleen, and testes after oral administration at both 1 and 3 mg/kg doses. Dose proportionality in tissue distribution was observed except for the kidneys. In conclusion, enavogliflozin can be administered without concern for pharmacokinetic changes, regardless of single or multiple dosing and whether in fed or fasted states. Furthermore, the tissue distribution profile may offer valuable insights into the therapeutic potential of this drug. |
| format | Article |
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| spelling | doaj-art-acf9f2ef7dcb417597d714b6ba16de402025-08-20T02:12:24ZengMDPI AGApplied Sciences2076-34172025-01-01153144510.3390/app15031445Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry MethodMinyeong Pang0Jihoon Lee1Min-Koo Choi2Im-Sook Song3College of Pharmacy, Dankook University, Cheon-an 31116, Republic of KoreaBK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Vessel-Organ Interaction Research Center (VOICE), College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaCollege of Pharmacy, Dankook University, Cheon-an 31116, Republic of KoreaBK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Vessel-Organ Interaction Research Center (VOICE), College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaEnavogliflozin, a sodium–glucose cotransporter 2 inhibitor, was approved in 2022 by the Korean Ministry of Food and Drug Safety as a therapeutic agent for type 2 diabetes mellitus and has been investigated for expanded therapeutic efficacy in diabetic retinopathy and cardioprotection. In this study, we developed and validated an analytical method to precisely detect enavogliflozin in mouse plasma, employing liquid–liquid extraction combined with liquid chromatography–tandem mass spectrometry. Overall, the analytical method, covering a range of 5–3000 ng/mL, is reliable for investigating the time-concentration profiles of enavogliflozin, demonstrating acceptable accuracy, precision, extraction recovery, and minimal matrix effects without stability concerns as evidenced by assessments of post-treatment stability, freeze–thaw stability, and short-term stability of enavogliflozin. Pharmacokinetic profiles and all pharmacokinetic parameters of enavogliflozin in mice did not differ between fed and fasted states after oral administration of enavogliflozin (1 mg/kg). Additionally, no differences in the pharmacokinetic profiles of enavogliflozin were observed among single, 7-day repeated, and 14-day repeated oral administrations at 1 mg/kg. In the tissue distribution study, enavogliflozin showed the highest distribution in the kidneys, followed by the large intestine, stomach, small intestine, liver, heart, lungs, spleen, and testes after oral administration at both 1 and 3 mg/kg doses. Dose proportionality in tissue distribution was observed except for the kidneys. In conclusion, enavogliflozin can be administered without concern for pharmacokinetic changes, regardless of single or multiple dosing and whether in fed or fasted states. Furthermore, the tissue distribution profile may offer valuable insights into the therapeutic potential of this drug.https://www.mdpi.com/2076-3417/15/3/1445enavogliflozinSGLT2 inhibitorLC-MS/MSanalytical validationpharmacokineticstissue distribution |
| spellingShingle | Minyeong Pang Jihoon Lee Min-Koo Choi Im-Sook Song Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry Method Applied Sciences enavogliflozin SGLT2 inhibitor LC-MS/MS analytical validation pharmacokinetics tissue distribution |
| title | Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry Method |
| title_full | Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry Method |
| title_fullStr | Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry Method |
| title_full_unstemmed | Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry Method |
| title_short | Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice Using a Validated Liquid Chromatography–Tandem Mass Spectrometry Method |
| title_sort | pharmacokinetics and tissue distribution of enavogliflozin in mice using a validated liquid chromatography tandem mass spectrometry method |
| topic | enavogliflozin SGLT2 inhibitor LC-MS/MS analytical validation pharmacokinetics tissue distribution |
| url | https://www.mdpi.com/2076-3417/15/3/1445 |
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