Metabolite identification and metabolic pathway analysis of pirtobrutinib in rats
- VernacularTitle:匹妥布替尼在大鼠体内的代谢产物鉴定及代谢途径分析
- Author:
Meijuan ZHANG
1
;
Jie LI
2
;
Hang YIN
1
;
Mengyu HOU
1
;
Jiangshuo LI
1
;
Jingxuan WU
1
;
Ruihua DONG
1
Author Information
1. Dept. of Research Ward，Beijing Friendship Hospital，Capital Medical University，Beijing 100050，China
2. School of Chinese Materia Medica，Beijing University of Chinese Medicine，Beijing 102488，China
- Publication Type:Journal Article
- Keywords:
pirtobrutinib;
metabolites;
metabolic pathway
- From:
China Pharmacy
2025;36(9):1076-1081
- CountryChina
- Language:Chinese
-
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.
