匹妥布替尼在大鼠體內(nèi)的代謝產(chǎn)物鑒定及代謝途徑分析
中圖分類號(hào)R969.1;R917 文獻(xiàn)標(biāo)志碼A 文章編號(hào)1001-0408（2025）09-1076-06
DOI10.6039/j.issn.1001-0408.2025.09.10
ABSTRACTOBJECTIVEToanalyzeandidentifythemetabolitesof pirtobrutinib（PTN）inrats，andclarifythe posible metabolic pathways of PTN in rats.METHODS Six rats were intragastrically administered with 1 0 m g / k g PTN suspension. Blood sampleswerecollctedfromtherats30minutesbeforeadministrationandat0.25，0.5，1，2，4，6，8，12，24hoursafter administration.Urineandfecessampleswerecolected12 hours beforeadministrationand24hoursafteradministration.UHPLOrbitrapExploris240systemcombined withCompoundDiscoverer3.0andXcalibur2.Osoftwarewereadoptedforstructural identificationandmetabolicpathwayanalysisofPTNmetabolitesinratplasma，urine，andfeces.RESULTSAtotalof29PTN metaboliteswereidentified，ncluding17，19and22metabolites inplasma，urineandfeces，respectively.Themetabolicpathways of PTNmainlyincludedoxidation，sulfation，gluuronidation，etc.，andits metaboliteswere mostlycombinationproductsof two ormorediferentmetabolicforms.Indetail，atotalof26metaboliteswereasociatedwithphaseImetabolicreactions（14 oxidationmetabolites，9reduction/dehydrogenationmetabolites，8demethylationmetabolites，and5hydrolysismetabolites）. Meanwhile，atotalof 20products were involved in phaseI metabolites （14 sulfation metabolitesand8glucuronic acid binding metabolites）.CONCLUSIONSPTNexhibitsadiverserangeof metabolites inratfecalsamples，withtheprimarymetabolic pathways being oxidation，sulfation，glucuronidation，and others.
KEYWORDS pirtobrutinib；metabolites；metabolic pathway
匹妥布替尼（pirtobrutinib，PTN）是一種新型的具有高選擇性、可逆性特點(diǎn)的非共價(jià)布魯頓氏酪氨酸激酶（Bruton'styrosinekinase，BTK）抑制劑[]。（剩余9438字）