Characterization of the metabolites of tirabrutinib generated from rat, dog and human liver microsomes using ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry
文献类型：期刊论文
| 作者 | Zhang, Hongjian1,2; Hu, Zhen3; Zhang, Huiping1,2; Sun, Xiyan1,2 ; Yang, Jianming4; Yuan, Jie5
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| 刊名 | RAPID COMMUNICATIONS IN MASS SPECTROMETRY
 |
| 出版日期 | 2022-03-15 |
| 卷号 | 36 |
| ISSN号 | 0951-4198 |
| DOI | 10.1002/rcm.9240 |
| 通讯作者 | Yang, Jianming(jmyang88@163.com) |
| 英文摘要 | Rationale Tirabrutinib is an orally administered Bruton's tyrosine kinase (BTK) inhibitor developed for the treatment of autoimmune disorders and haematological malignancies. The goals of this study were to identify the metabolites of tirabrutinib and to propose the metabolic pathways. Methods Tirabrutinib was individually incubated with rat, dog and human liver microsomes at 37 degrees C for 1 h. To trap the potential reactive metabolites, glutathione (GSH) was incorporated into the incubation samples. The incubation samples were analysed using ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry (UHPLC-HRMS). The metabolites were identified and characterized by exact masses, product ions and retention times. Results A total of 18 metabolites, including four GSH conjugates, were identified and characterized in terms of elemental compositions and product ions. The metabolic pathways of tirabrutinib included amide hydrolysis, O-dealkylation, mono-oxygenation, di-oxygenation and GSH conjugation. Among these metabolites, M10 was the most abundant metabolite. Compared with dog, rat has the closer metabolic profiles to humans, and thus it would be more suitable for toxicity study. Conclusions This study provides valuable data regarding the in vitro metabolism of tirabrutinib, which may be helpful for further safety assessment of this drug. |
| WOS关键词 | DRUG-METABOLISM ; DISCOVERY |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Spectroscopy |
| 语种 | 英语 |
| WOS记录号 | WOS:000759654400002 |
| 出版者 | WILEY |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/127954]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Yang, Jianming |
| 作者单位 | 1.Chinese Acad Sci, Hefei Canc Hosp, Dept Otorhinolaryngol Head & Neck Surg, Hefei, Peoples R China 2.Chinese Acad Sci, Hefei Inst Phys Sci, Inst Hlth & Med Technol, Anhui Prov Key Lab Med Phys & Technol, Hefei, Peoples R China 3.Anhui Med Univ, Hosp 2, Dept Radiol, Hefei, Peoples R China 4.Anhui Med Univ, Hosp 2, Dept Otorhinolaryngol Head & Neck Surg, 678 Furong Rd, Hefei 230601, Anhui, Peoples R China 5.Anhui Prov Inst Food & Drug Control, Hefei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Hongjian,Hu, Zhen,Zhang, Huiping,et al. Characterization of the metabolites of tirabrutinib generated from rat, dog and human liver microsomes using ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry[J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY,2022,36. |
| APA | Zhang, Hongjian,Hu, Zhen,Zhang, Huiping,Sun, Xiyan,Yang, Jianming,&Yuan, Jie.(2022).Characterization of the metabolites of tirabrutinib generated from rat, dog and human liver microsomes using ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry.RAPID COMMUNICATIONS IN MASS SPECTROMETRY,36. |
| MLA | Zhang, Hongjian,et al."Characterization of the metabolites of tirabrutinib generated from rat, dog and human liver microsomes using ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry".RAPID COMMUNICATIONS IN MASS SPECTROMETRY 36(2022). |
入库方式： OAI收割
来源：合肥物质科学研究院
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