Objective:To conduct a comparative study on the brain pharmacokinetics of seven ingredients(i.e.senkyunolide A,ferulic acid,formononetin,calycosin,ononin,calycosin-O-β-D-glucopyranoside,and paeoniflorin),which were the compounds of Buyang Huanwu Decoction(BHD),in normal and cerebral ischemia rats administrated intragastrically with BHD.Methods:The samples of normal and permanent middle cerebral artery occlusion(pMCAO)rats were col-lected by using brain microdialysis technique.The concentrations of seven ingredients were determined by the HPLC-MS/MS method.After the BHD were administrated intragastrically to the rats for seven con-secutive days,brain microdialysis probes were inserted into the hippocampus of rats,and then the brain microdialysates were collected at 20 min time intervals for 5 h.The separation of the seven ingredients and internal standard(IS)was carried out on an ACQUITY UPLC BEH C18(2.1 mm x 100 mm,1.7 μm)chromatographic column,using a mobile phase consisting of acetonitrile(containing 0.1％formic acid)and water(containing 0.1％formic acid)for gradient elution within 13 min.The ionization was conducted using an ESI source in positive ion mode.Multiple reaction monitoring mode was used for quantification of ingredients in BHD.Results:Linearity,accuracy,precision,matrix effect and stability of LC-MS/MS method were all satisfac-tory,successfully applied to compare the pharmacokinetics of the analytes between normal and model rats after intragastric administration of BHD.Compared with the normal group,the model group after the administration of the BHD showed that T1/2 of formononetin and ononin were longer,and except for calycosin-O-β-D-glucopyranoside(P＜0.01),there was no significant difference between the normal group and the model group.The Cmax of senkyunolide A and calycosin of model group were increased,while the Tmax of senkyunolide A was decreased,and except for the Tmax of PF,the differences between the two groups were statistically significant(P＜0.01).Conclusion:The LC-MS/MS method combined with microdialysis was successfully applied to the compar-ative study of brain pharmacokinetics of seven ingredients in BHD.After intragastric administration of BHD,there were differences in the pharmacokinetics of seven ingredients in the brain hippocampus between normal rats and model rats,probably related to the characteristics of the ingredients and the effects of cerebral ischemia on the absorption and distribution of the ingredients.

College of Chinese Materia Medica,Guangzhou University of Chinese Medicine,Guangzhou 510006,China

[1]Wanyi Liu;Keqi Zeng;Xin Zhou;Yingfeng Zhang;Cong Nie-.Comparative study on brain pharmacokinetics of Buyang Huanwu Decoction in normal and cerebral ischemia rats using brain microdialysis combined with LC-MS/MS)[J].中草药（英文版）,2022(04):630-637

microdialysis,senkyunolide,ononin,microdialysates

Comparative,study,brain,pharmacokinetics,Buyang,Huanwu,Decoction,normal,cerebral,ischemia,rats,using,combined,Objective,To,comparative,seven,ingredients,ferulic,acid,formononetin,calycosin,glucopyranoside,paeoniflorin,which,were,compounds,BHD,administrated,intragastrically,Methods,samples,permanent,middle,artery,occlusion,pMCAO,by,technique,concentrations,determined,HPLC,method,After,secutive,days,probes,inserted,into,hippocampus,then,collected,intervals,separation,internal,standard,IS,was,carried,out,ACQUITY,UPLC,BEH,C18,chromatographic,column,mobile,phase,consisting,acetonitrile,containing,formic,water,gradient,elution,within,ionization,conducted,ESI,source,positive,Multiple,reaction,monitoring,used,quantification,Results,Linearity,accuracy,precision,matrix,stability,satisfac,tory,successfully,applied,compare,analytes,between,model,after,administration,Compared,showed,that,longer,except,there,significant,Cmax,increased,while,Tmax,decreased,PF,differences,two,groups,statistically,Conclusion,probably,related,characteristics,effects,absorption,distribution

0.391814