Studyon Pharmacokinetics Markers Compound Danshen Dropping Pills In Healthy Volunteers

Objective:This article mainly aimed at the compound danshen dropping pills of salvia miltiorrhiza and notoginseng parts marked of pharmacokinetic study in healthy volunteers,clarify pharmacokinetic characteristics of compound danshen dropping pills,it is concluded that the main pharmacokinetic parameters,further deepening the understanding of the body process of compound danshen dropping pills,which for security,compatibility of compound danshen dropping pills formula is scientific to provide theoretical basis.Methods:(1)Established the topic in biological samples(plasma/urine)of compound danshen dropping pills salvia miltiorrhiza and notoginseng medicine generation of labeled objects of LC-MS/MS detection method and the specificity of the two methods,linear,precision,accuracy,recovery rate and stability was investigated,and choose different proportion of mobile phase conditions and optimize the best mass spectrometry detection of two kinds of medicine generation of labeling,can satisfy human pharmacokinetic studies.(2)12 of male healthy volunteers,fasting 12 hours(give water)for the night.The next morning,fasting administration.200ml warm water was given.Reference of clinical medication doses,1 hour after taking the drug can be a suitable amount of drinking water,eating 3 hours last in unity.Before delivery and 5’after the treatment,10,20’,40’,1 h,1.5 h,2 h,3 h,4 h,6 h,8 h,12 h and 24 h gathering volunteers right forearm venous indwelling tube in pursuance of 3 ml,put the whole blood collected in prepared heparinization in vitro,constant temperature 4℃ centrifuge for 10 min(4500rpm),transfer the upper plasma and 10ml ep tube.(3)The blood drug concentration-time data and urine cumulative dose-time data by DAS2.0 pharmacokinetic software according to the atrioventricular model processing,computational medicine generation of labeled objects in the main pharmacokinetic parameters in the human body.Results:(1)Establishment of a rapid,sensitive and convenient two LC-MS/MS method to detect the plasma in the urine of salvia miltiorrhiza and notoginseng medicine labeled concentration,were confirmed by methodology method meets the requirements.(2)12 of male healthy volunteers after oral compound salvia miltiorrhiza preparation,salvia miltiorrhiza some medicine generation of labeled objects(DSS,HMPLA,PCA and PAA)in vivo pharmacokinetic parameters:Tmax(min)were 0.7±0.2、0.9±0.3、2.5±3.1、0.3±0.1;Cmax(ng/mL)were 131.8±45.46、67.46±55.30、34.59±51.43、119.49±149.58;T1/2(min)were 3.69±4.91、9.95±10.09、26.23±14.89;AUC0-t(ng min/mL)were 215.20±58.26、136.28±35.04、78.37±114.80、102.97±87.53;MRT(min)were 2.15±0.68、3.64±0.87、10.17±6.06、5.94±10.47;Notoginseng some medicine generation of labeled objects(NR1,Rg1,Rbl)in vivo pharmacokinetic parameters:Tmax(min)were 0.74±0.46、0.37±0.22、2.17±2.11;Cmax(ng/mL)were 0.67±0.44、2.34±1.17、8.68±5.63;T1/2(min)were 2.98±2.94、5.06±6.32、13.61±8.79;AUC0-t(ng min/mL)were 0.69±0.35、5.29±2.32、94.09±76.73;MRT(min)were 4.02±4.24、6.78±8.10、20.28±10.63;(3)Protocatechualdehyde and Ginsenoside Rb1 are not detected.In the urine,12 to 24 h period of urine samples,DSS,4-hydroxy-3-methoxy phenyl lactic acid,protocatechuic acid urine dosage,respectively,2098±648.19ng;1582.66±559.77ng;468.04±203.44ng;R1 and Rgl urinedosage,respectively,6883.77±5682.80ng24518.94±22970.89ng。Conclusion:(1)The experiment established the salvia miltiorrhiza and notoginseng parts,respectively,labeled liquid ms determination method,according to the methodology validation requirements to verify this method,the test items are conform to the rules,the method can be used for human pharmacokinetic studies.(2)In human blood samples were measured with and its metabolites 4-hydroxy-3-methoxy phenyl lactic acid,protocatechuic acid,protocatechuic aldehyde and its metabolites,notoginseng saponin R1 and ginseng saponin Rgl and ginseng saponin Rbl of 7 kinds of ingredients,and AUC exposure levels reach a certain body.In human urine,because of protocatechuic aldehyde and ginseng saponin Rb1 hardly pass urine excretion,cannot be determined accurately,the other 5 kinds of composition can be determined accurately.(3)According to the literature and our study,choose the effects of exposure quantity(AUC)in the body composition as medicine generation of labeling,and protocatechuic aldehyde,panax notoginseng saponins R1 and ginseng saponin Rgl and ginseng saponin Rbl these 5 kinds of prototype components have cardiovascular activity,so choose its metabolites 4-hydroxy-3-methoxy phenyl lactic acid,protocatechuic acid,protocatechuic aldehyde and its metabolites of these four components as compound danshen dropping pills salvia miltiorrhiza part of medicine generation of labeling,choose notoginseng saponin R1,ginseng saponin Rgl and ginseng saponin Rbl three ingredients as part of notoginseng drug labeling.