清热凉血方大鼠体内分布特征分析  

Distribution Characteristics of Qingre Liangxue Formula in Rats

作　　者：刘家邑 白彦萍[2] 蔡锐 周相男 刘军锋 LIU Jiayi;BAI Yanping;CAI Rui;ZHOU Xiangnan;LIU Junfeng(China-Japan Friendship Clinical Medical College,Beijing University of Chinese Medicine,Beijing,China 100029;China-Japan Friendship Hospital,Beijing,China 100029;Shaanxi Hospital of Traditional Chinese Medicine,Xi'an,Shaanxi,China 710003)

机构地区：[1]北京中医药大学中日友好临床医学院,北京100029 [2]中日友好医院,北京100029 [3]陕西省中医医院,陕西西安710003

出　　处：《中国药业》2024年第20期51-57,共7页China Pharmaceuticals

基　　金：国家自然科学基金[82074445];国家中医药管理局岐黄学者支持项目[国中医药人教函〔2022〕6号]。

摘　　要：目的探讨清热凉血方在大鼠体内的分布特征。方法采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法,色谱柱为Thermo Accucore aQ C_(18)柱(150 mm×2.1 mm,2.6μm),流动相为甲醇-0.1%甲酸水溶液(梯度洗脱),流速为0.3 mL/min,柱温为35℃,进样量为3μL。离子源为加热电喷雾离子源(HESI),喷雾电压为3.5 kV,鞘气(N2)流量40 arb,辅助气(N2)流量10 arb,辅助加热器温度350℃,毛细管温度320℃。扫描方式采用正、负离子全扫描/数据依赖的二级子离子扫描(Full MS/dd-MS2)模式,扫描范围m/z 100~1500,碰撞能量30 eV。予大鼠灌胃清热凉血方(93.6 g/kg),每日1次,连续4 d。于给药后不同时间点采集血浆、不同组织及排泄物,鉴定原型成分分布特征。结果共鉴定入体成分18种,排泄物22种,其中末次给药后0.5 h、1 h、1.5 h、2 h时大鼠血浆样品中分别检出10种、4种、6种、7种清热凉血方的原型成分;末次给药后2 h时心、肝、脾、肺、肾、脑组织中分别检测到9种、7种、7种、5种、7种、9种原型成分;第3日给药后8 h至第4日给药前粪便和尿液中分别检测到11种和15种原型成分。结论该研究对清热凉血方中入体成分进行了全面鉴定和分析,为其后续质量评价、药效物质及作用机制等研究奠定了一定基础。Objective To investigate the distribution characteristics of Qingre Liangxue Formula in rats.Methods The ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitaltrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS)was adopted.The chromatographic column was the Thermo Accucore aQ C_(18)column(150 mm×2.1 mm,2.6μm),the mobile phase was methanol-0.1%formic acid aqueous solution(gradient elution),the flow rate was 0.3 mL/min,the column temperature was 35℃,and the injection volume was 3μL.The heating electrospray ionization(HESI)was adopted,the spray voltage was 3.5 kV,the sheath gas(N2)flow rate was 40 arb,the auxiliary gas(N2)flow rate was 10 arb,the auxiliary heater temperature was 350℃,and the capillary temperature was 320℃.The Full MS/dd-MS2 mode with positive and negative ions was adopted,with a scanning range of m/z 100-1500 and collision energy of 30 eV.The rats were given Qingre Liangxue Formula(93.6 g/kg)by gavage once a day for 4 d.The plasma,different tissues and excreta were collected at different time points after administration to identify the distribution characteristics of prototype components.Results A total of 18 prototype components in vivo and 22 prototype components in excreta were identified.Ten,four,six,seven prototype components of the Qingre Liangxue Formula were detected in rat plasma samples at 0.5 h,1 h,1.5 h and 2 h after the last administration,respectively.Nine,seven,seven,five,seven,nine prototype components were detected in the heart,liver,spleen,lung,kidney,brain tissues at 2 h after the last administration,respectively.Eleven and fifteen prototype components were detected in the feces and urine from 8 h after administration on the 3rd day to before administration on the 4th day,respectively.Conclusion The components in vivo of Qingre Liangxue Formula are comprehensively identified and analyzed in this study,and the study can lay a foundation for the subsequent quality evaluation and studies on pharmacological substances and mechanisms

关 键 词：超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法 清热凉血方 原型成分 体内分布 药效物质 

分 类 号：R917[医药卫生—药物分析学]