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匹妥布替尼在大鼠体内的代谢产物鉴定及代谢途径分析
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| 篇名： | 匹妥布替尼在大鼠体内的代谢产物鉴定及代谢途径分析 |
| TITLE： | Metabolite identification and metabolic pathway analysis of pirtobrutinib in rats |
| 摘要： | 目的 分析、鉴定匹妥布替尼（PTN）在大鼠体内的代谢产物，并探讨其在大鼠体内的可能代谢途径。方法6只大鼠按照10mg/kg灌胃PTN混悬液，收集大鼠给药前30min以及给药后0.25、0.5、1、2、4、6、8、12、24h的血液和给药前12h及给药后24h的尿液和粪便。采用UHPLC-OrbitrapExploris240系统联合CompoundDiscoverer3.0和Xcalibur2.0数据分析软件对PTN在大鼠血浆、尿液和粪便中的代谢产物进行结构鉴定与代谢途径分析。结果在大鼠生物样本中共鉴定出29种PTN代谢产物，在血浆、尿液和粪便样本中分别鉴定出17、19和22种代谢产物。PTN的代谢途径主要包括氧化、硫酸化、葡萄糖醛酸化等，且其代谢产物多为2种及以上不同代谢形式的组合产物。其中，涉及Ⅰ相代谢反应的产物共计26个（氧化14个、还原/脱氢9个、脱甲基8个、水解5个），涉及Ⅱ相代谢反应的产物共计20个（硫酸化14个、葡萄糖醛酸化8个）。结论PTN在大鼠粪便样本中代谢产物种类较多，主要代谢途径为氧化、硫酸化、葡萄糖醛酸化等。 |
| ABSTRACT： | OBJECTIVE To analyze and identify the metabolites of pirtobrutinib （PTN） in rats， and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma， urine， and feces. RESULTS A total of 29 PTN metabolites were identified， including 17， 19 and 22 metabolites in plasma， urine and feces， respectively. The metabolic pathways of PTN mainly included oxidation， sulfation， glucuronidation， etc.， and its metabolites were mostly combination products of two or more different metabolic forms. In detail， a total of 26 metabolites were associated with phase Ⅰ metabolic reactions （14 oxidation metabolites， 9 reduction/dehydrogenation metabolites， 8 demethylation metabolites， and 5 hydrolysis metabolites）. Meanwhile， a total of 20 products were involved in phase Ⅱ metabolites （14 sulfation metabolites and 8 glucuronic acid binding metabolites）. CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples， with the primary metabolic pathways being oxidation， sulfation， glucuronidation， and others. |
| 期刊： | 2025年第36卷第09期 |
| 作者： | 张美娟；李洁；尹航；侯梦雨；李江硕；吴竞轩；董瑞华 |
| AUTHORS： | ZHANG Meijuan，LI Jie，YIN Hang，HOU Mengyu，LI Jiangshuo，WU Jingxuan，DONG Ruihua |
| 关键字： | 匹妥布替尼；代谢产物；代谢途径 |
| KEYWORDS： | pirtobrutinib； metabolites； metabolic pathway |
| 阅读数： | 5 次 |
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