痛舒胶囊临床最大耐受剂量实验中4种成分药物浓度测定方法建立  

The Method of Determination of the concentration of 4 ingredients in the clinical MTD experiment of Tongshu capsule

作　　者：赵高琼 刘红斌 崔佳丽 梅晶 周艺佳 王京昆 ZHAO Gaoqiong;LIU Hongbin;CUI Jiali;MEI Jing;ZHOU Yijia;WANG Jingkun(Yunnan Institute of Materia Medica,Kunming 650111,China;Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation,Kunming 650111,China)

机构地区：[1]云南省药物研究所,云南昆明650111 [2]云南省中药和民族药新药创制企业重点实验室,云南昆明650111

出　　处：《中国民族民间医药》2022年第13期21-25,共5页Chinese Journal of Ethnomedicine and Ethnopharmacy

基　　金：云南省科技厅“院士及科技领军人才专项-科技领军人才”项目基金资助项目(2014HA001)。

摘　　要：目的:建立痛舒胶囊中指标性成分栀子苷、人参皂苷Rg1、三七皂苷R1、人参皂苷Rb1在人血浆中的LC-MS/MS浓度检测方法,并对该方法进行验证,以经过验证的方法,对来自痛舒胶囊临床MTD(最大耐受量)实验的血浆样本进行药物浓度检测,获得志愿者口服给予痛舒胶囊后体内的药物浓度水平。方法:色谱柱:Waters SunFire C 18(4.6 mm×150 mm,5μm);流动相:A为0.01%甲酸水,B为甲醇;梯度洗脱:0~1 min,90%A;1~8 min,90%~10%A;8~10 min,10%A;10~10.5 min,10%~90%A;10.5~15 min,90%A。流速:1 mL/min。柱温:20℃;进样量:10μL。离子源:ESI源,正离子模式,MRM扫描。结果:栀子苷、人参皂苷Rg1、三七皂苷R1、人参皂苷Rb1及内标盐酸普萘洛尔提取离子色谱图与血浆中内源性杂质互不干扰。以盐酸普萘洛尔为内标,栀子苷、人参皂苷Rg1、三七皂苷R1、人参皂苷Rb1的检测范围分别为252~8100 ng/mL、26.8~858 ng/mL、32.8~1050 ng/mL、11.2~361 ng/mL。各成分日内精密度与日间精密度RSD≤15%,准确度分别在85%~115%之间,提取回收率在61.05%~96.54%之间。基质对4个成分各浓度间的影响基本一致。结论:该方法快速、灵敏、重复性好,可用于痛舒胶囊中4种有效成分在人体内的MTD试验样本药物浓度检测。Objective To establish a method that detect the concentration of major components:geniposide,ginsenoside Rg1,notoginsenoside R1 and ginsenoside Rb1 of Tongshu capsule in human plasma utilizing LC-MS/MS,then validate this methodology.With proven methods,detecting drug concentration in plasma samples form volunteers that experienced clinical MTD(Maximum Tolerance Dose)experiment,Tongshu capsule dosed orally.Methods The chromatographic column:Waters Sun Fire C18(4.6 mm×150 mm,5μm).Mobile phase:A is 0.01%formic water,B is methanol.Gradient elution:0-1 min,90%A;8-10 min,10%A;10-10.5 min,10%-90%A;10.5-15 min,90%A.Flow rate:1 mL·min-1.Column temperature:20℃.Injection volume:10μL.Ion source:ESI,positive ion mode,MRM scan.Results The ion chromatograms of geniposide,ginsenoside Rg1,notoginsenoside R1,ginsenoside Rb1 and internal standard of Propranolol hydrochloride were not interfered with the endogenous impurities in the plasma.The detection ranges of Geniposide,ginsenoside Rg1,notoginsenoside R1 and ginsenoside Rb1 were 252-8100 ng/mL,26.8-858 ng/mL,32.8-1050 ng/mL and 11.2-361 ng/mL.Respectively,The inday precision and day precision RSD of each component was≤15%,the accuracy ranged from 85% to 115%,and the extraction recovery ranged from 61.05% to 96.54%.The effects of substrate on the concentrations of the four components were basically consistent.Conclusion This method is rapid,sensitive and reproducible,and can be used to detect the concentration of 4 active ingredients in tongshu capsule in human MTD test samples.

关 键 词：痛舒胶囊 栀子苷 人参皂苷Rg1 三七皂苷R1 人参皂苷RB1 

分 类 号：R284.1[医药卫生—中药学]