匹妥布替尼在大鼠体内的代谢产物鉴定及代谢途径分析

中图分类号R969.1;R917 文献标志码A 文章编号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）是一种新型的具有高选择性、可逆性特点的非共价布鲁顿氏酪氨酸激酶（Bruton'styrosinekinase，BTK）抑制剂[]。（剩余9438字）