Characterization and quantitative determination of henagliflozin metabolites in humans
文献类型：期刊论文
| 作者 | Chen, Zhendong1; Li, Liang1 ; Zhan, Yan1; Zhang, Yifan1; Liu, Haiyan2; Zou, Jianjun2; Zhong, Dafang1
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| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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| 出版日期 | 2021-01-05 |
| 卷号 | 192页码:8 |
| 关键词 | Henagliflozin Metabolism LC-MS/MS |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2020.113632 |
| 通讯作者 | Zhong, Dafang(dfzhong@simm.ac.cn) |
| 英文摘要 | Henagliflozin is a highly specific inhibitor of sodium-glucose co-transporter-2 (SGLT2) proposed as a more efficient medication for type 2 diabetes mellitus (T2DM). In this work, henagliflozin metabolic profile was investigated in human plasma and urine samples using a newly developed high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC/Q-TOF MS) method. A total of 8 metabolites were observed, while the structures of four major metabolites, including M1 (O-deethylation metabolite), M5-1 (2-O- beta-glucuronide conjugate), M5-2 (6-O-beta-glucuronide conjugate), and M5-3 (3-O-beta-glucuronide conjugate) were confirmed in our study after comparison with the reference standards. The principal henagliflozin metabolic pathways were identified as glucuronidation and O-deethylation in humans. The principal form of henagliflozin in human plasma was parent drug, followed by M5-1; while it was M5-3 and M5-1 in urine. Subsequently, an accurate and simple LC-MS/MS method was developed for simultaneously determine M5-1, M5-2, and M5-3 in human plasma. After optimization of this method, three M5 isomers were successfully separated and quantified using chromatography. Acetonitrile-induced protein precipitation method was adapted for extracting the analytes from human plasma. Separation was conducted using Gemini C-18 column under gradient elution with 5 mM aqueous ammonium acetate (A) and acetonitrile (B) mobile phases. Negative electrospray ionization was conducted using a selective reaction monitoring with the same transition of m/z 629 -> 321 for detection of three M5 isomers. The method showed good linearities for M5-1, M5-2, and M5-3 within the range of 1.00-150 ng/mL, 0.500-75.0 ng/mL, and 1.00-150 ng/mL, respectively. Conclusively, the method has been applied successfully to assess phase I henagliflozin pharmacokinetics and pharmacodynamics and providing effective safety evaluations. (C) 2020 Elsevier B.V. All rights reserved. |
| WOS关键词 | COTRANSPORTER 2 INHIBITOR ; SGLT2 INHIBITORS ; PHARMACOKINETICS ; PHARMACODYNAMICS ; MORINIDAZOLE ; METFORMIN ; DISEASE |
| 资助项目 | Chinese Academy of Sciences[XDA12050306] ; National Natural Science Foundation of China[81521005] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000600772100004 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296025]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Reseach, Shanghai 201210, Peoples R China 2.Jiangsu Hengrui Med Co Ltd, Shanghai 201210, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Zhendong,Li, Liang,Zhan, Yan,et al. Characterization and quantitative determination of henagliflozin metabolites in humans[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2021,192:8. |
| APA | Chen, Zhendong.,Li, Liang.,Zhan, Yan.,Zhang, Yifan.,Liu, Haiyan.,...&Zhong, Dafang.(2021).Characterization and quantitative determination of henagliflozin metabolites in humans.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,192,8. |
| MLA | Chen, Zhendong,et al."Characterization and quantitative determination of henagliflozin metabolites in humans".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 192(2021):8. |
入库方式： OAI收割
来源：上海药物研究所
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