代谢分析

HPLC-MS/MS 测定龙生蛭胶囊在大鼠血浆中 7 个活性成分的含量及其药代动力学研究*

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  • 1.石河子大学药学院,石河子 832002;
    2.北京中医药大学中药分析与转化研究中心,北京 100029;
    3.北京中医药大学 北京中医药研究院,北京 100029;
    4.北京中医药大学中药学院,北京 100029;
    5.北京中医药大学中医学院,北京 100029
第一作者:Tel:18801383744;E-mail:jyang5208@163.com
** 肖红斌 Tel:(010)64286490;E-mail:hbxiao69@163.com ;王 伟 Tel:(010)64286283;E-mail:wangwei26960@126.com

收稿日期: 2021-02-06

  网络出版日期: 2024-07-11

基金资助

* 国家自然科学基金项目(81703947,81774155)

Determination of seven components of Longshengzhi capsules in rat plasma by HPLC-MS/MS and its application in pharmacokinetic study*

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  • 1. School of Pharmacy,Shihezi University,Shihezi 832002,China;
    2. Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine,Beijing 100029,China;
    3. Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;
    4. School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029, China;
    5. School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China

Received date: 2021-02-06

  Online published: 2024-07-11

摘要

目的: 建立龙生蛭胶囊在血浆中活性成分的定量分析方法,并对各成分进行药代动力学研究。方法: 采用HPLC-MS/MS 分析方法,使用Agilent Rapid Resolution HD C18 色谱柱(50 mm×2.1 mm, 1.8 μm),流动相为乙腈- 水(含0.1% 甲酸),梯度洗脱,流速0.5 mL·min-1;采用电喷雾离子源,分别选择正或负离子模式进行多反应监检测扫描(MRM),分析时间正离子模式下6 min,负离子模式下3 min。结果: 经方法学验证,各成分线性关系良好(r>0.997 7),提取回收率在85.1%~114.5% 范围内,基质效应在85.08%~112.95% 范围内,日内精密度RSD<10%,日间精密度RSD<9.6%,稳定性RSD<13%,均符合生物样品分析要求,满足大鼠血浆样品中各成分分析测定的需求。用DAS 3.0 软件计算龙生蛭胶囊的7 个活性成分在大鼠体内的药代动力学参数。结果表明,苦杏仁苷、阿魏酸、异嗪皮啶、毛蕊异黄酮、洋川芎内酯A、氧化芍药苷、芍药苷的达峰时间(Tmax)分别为(0.36±0.31)h、(0.11±0.05)h、(0.10±0.04)h、(3.36±3.69) h、(1.07±0.80)h、(2.35±3.12)h、(0.60±0.44)h;消除半衰期(t1/2)分别为(1.02±0.46)h、(7.95±10.74) h、(32.55±15.57)h、(3.67±2.07)h、(1.19±0.12)h、(2.39±1.92)h、(1.50±0.12)h。结论: 该研究为龙生蛭胶囊主要成分的药理活性研究及临床用药提供科学数据。

本文引用格式

杨洁, 贾志鑫, 刘洁, 李月婷, 陈奕君, 王伟, 肖红斌 . HPLC-MS/MS 测定龙生蛭胶囊在大鼠血浆中 7 个活性成分的含量及其药代动力学研究*[J]. 药物分析杂志, 2021 , 41(7) : 1176 -1188 . DOI: 10.16155/j.0254-1793.2021.07.09

Abstract

Objective: To establish a method for quantitative analysis of active components in plasma of Longshengzhi capsules and to study the pharmacokinetic of each component. Methods: Using HPLC-MS/MS analysis method,Agilent Rapid Resolution HD C18 column( 2.1 mm×50 mm,1.8 μm) was adopted and the mobile phase was acetonitrile-water( containing 0.1% formic acid) with gradient elution at a flow rate of 0.5 mL·min-1. The electrospray ion source was adopted,and the positive or negative ion mode for multiple reaction detection scan( MRM) was selected. In detection mode,the analysis time was 6 min in positive ion mode and 3 min in negative ion mode. Results: Methodologically verified,the linear relationship of each component was good(r>0.997 7), the extraction recoveries were in the range of 85.1%-114.5%. The matrix effect was in the range of 85.08%-112.95%, the RSD values for intra-day precision,inter-day precision and stability were below 10%,9.6% and 13%,respectively. They all met the requirements of biological sample analysis and the requirements of analysis and determination of various components in rat plasma samples. The pharmacokinetic parameters of the 7 active ingredients of Longshengzhi capsules in rats were calculated by DAS 3.0 software. The results showed that the peak time( Tmax) of amygdalin,ferulic acid, isofraxidin,calycosin,senkyunolide A,oxypaeoniflora,and paeoniflorin was( 0.36±0.31)h and( 0.11±0.05)h, (0.10±0.04)h,(3.36±3.69)h,(1.07±0.80)h,(2.35±3.12)h and( 0.60±0.44)h,respectively. The elimination half-life( t1/2) was( 1.02±0.46)h,(7.95±10.74)h,(32.55±15.57)h,(3.67±2.07)h,(1.19±0.12)h, (2.39±1.92)h and( 1.50±0.12)h,respectively. Conclusion: This study provides scientific data for the study of pharmacological activity and clinical use of the main components of Longshengzhi capsules.

参考文献

[1] 魏紫奕,徐文娟,刘洁,等.基于HPLC-QQQ/MS 的龙生蛭胶囊中19 种代表性成分含量一致性分析[J].中国中药杂志,2019,44(5):948
WEI ZY,XU WJ,LIU J,et al .Simultaneous quantification and consistency analysis of 19 representative components in Longshengzhi Capsules by HPLC-QQQ/MS[J].China J Chin Mater Med,2019,44(5):948
[2] HU LF,YAO ZH,QIN ZF,et al.In vivo metabolic profiles of Bu-Zhong-Yi-Qi-Tang,a famous traditional Chinese medicine prescription,in rats by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry[J].J Pharm Biomed Anal,2019,171:81
[3] MA K,LI RW,ZHAO HL,et al.Cattle encephalon glycoside and ignotin reduce early brain injury and cognitive dysfunction after subarachnoid hemorrhage in rats[J].Neuroscience,2018,388: 181
[4] 康宁芳,李梅,胡贺佳,等.UPLC-MS/MS 同时测定舒肝宁注射液在大鼠血浆中4 种活性成分的含量及其药代动力学研究[J]. 中国中药杂志,2020,45(11):2626
KANG NF,LI M,HU HJ,et al.Simultaneous determination of of four active components of Shuganning injection in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study[J]. China J Chin Mater Med,2020,45(11):2626
[5] 贺敏,王猛猛,吴雨,等.补中益气汤6 个成分在大鼠体内的药代动力学研究[J].辽宁中医杂志,2020,47(11):159
HE M,WANG MM,WU Y,et al.Pharmacokinetic study of multiple active components from Buzhong Yiqi decoction after oral administration in rats by LC-MS /MS[J].Liaoning J Tradit Chin Med,2020,47(11):159
[6] 宋祯彦,何攀,李富周,等.高效液相色谱串联质谱法测定当归芍药散提取物和含药血清中3 种活性成分含量[J].中国中医药信息杂志,2021,28(1):92
SONG ZY,HE P,LI FZ,et al.Content determination of three active components in Danggui Shaoyao powder extracts and its drug-containing serum by HPLC-MS/MS[J].Chin J Inf Tradit Chin Med,2021,28(1):92
[7] ZHU L,SUN S,HU Y,et al.Metabolic study of paeoniflorin and total paeony glucosides from Paeoniae Radix Rubra in rats by high performance liquid chromatography coupled with sequential mass spectrometry(UPLC-ESI-MS)[J].Biomed Chromatogr,2018,32(4):1
[8] 靳志东,李科,李爱平,等.黄芪建中汤及其组方单味药化学成分与体内代谢研究进展[J].中草药,2019,50(18):4495
JIN ZD,LI K,LI AP,et al.Research progress on chemical composition and metabolism of Huangqi Jianzhong decoction and its constituent herbal medicines[J].Chin Tradit Herb Drugs,2019, 50(18):4495
[9] 范婷,李倩,姚欢.异嗪皮啶在大鼠体内的药物动力学研究及其组织分布[J]. 中国药师,2020,23(12):2371
FAN T,LI Q,YAO H.Studies on pharmacokinetics and distribution of isofraxidin in rats[J].China Pharm,2020,23(12):2371
[10] 赵睁睁,周严严,容蓉,等.芎汤超临界提取物中藁本内酯、正丁基苯酞和洋川芎内酯A 在大鼠体内排泄动力学[J].中国实验方剂学杂志,2015,21(3):80
ZHAO ZZ,ZHOU YY,RONG R,et al.Excretion kinetics of ligustilide,butylphthalide and senkyunolide A in supercritical CO2 extraction part from in rats[J].Chin J Exp Tradit Med Form,2015, 21(3):80
[11] WANG Y,LIU L,MA Y,et al.Chemical discrimination of Astragalus mongholicus and Astragalus membranaceus based on metabolomics using UHPLC-ESI-Q-TOF-MS/MS approach[J]. Molecules,2019,24(22):4064
[12] LI YT,LIU J,SU RB,et al.Pseudotargeted screening and determination of constituents in Qishen granule based on compound biosynthetic correlation using UHPLC coupled with high-resolution MS[J].J Sep Sci,2020,43:1032
[13] 刘湘丹,黄攀,卢岳华,等.补肾通络方中马钱苷、阿魏酸和二苯乙烯苷的体内药代动力学研究[J].中国中药杂志,2015,40(12):2428
LIU XD,HUANG P,LU YH,et al.Pharmacokinetics of loganin, ferulic acid and stilbene glucoside in Bushen Tongluo formula in vivo[J].China J Chin Mater Med,2015,40(12):2428
[14] 钟应淮,奉建芳,夏明艳,等.UPLC-MS/M 测定茶芎苯酞类有效部位及其β-CD 包合物中5 种成分的药动学研[J].中国中药杂志,2021,46(04):972
ZHONG YH,FENG JF,XIA MY,et al.Pharmacokinetic study of five components in phthalide target areas of Chaxiong and its inclusion compunds by UPLC-MS/MS[J].China J Chin Mater Med,2021,46(4):972
[15] CHEN SY,LIN Y,MIAO LH,et al.Ferulic acid alleviates lipopolysaccharide-induced acute liver injury in Megalobrama amblycephala[J].Aquaculture,2021,532:735972
[16] GAO ZW,HUANG Y,ZHANG JQ,et al.Paeoniflorin elicits the anti-proliferative effects on glioma cell via targeting translocator protein 18 Kda[J].J Pharm Sci,2021,145(1):115
[17] 雷甜甜. 苦杏仁苷抑制LDLR-/- 小鼠动脉粥样硬化的作用及机制研究[D].成都:电子科技大学,2020
LEI TT.The Inhibiting Effect and Possible Mechanisms of Amygdalin on Atherosclerosis in LDL Receptor-deficient Mice[D].Chengdu: University of Electronic Science and Technology of China,2020
[18] JIN L,YING ZH,YU CH,et al.Isofraxidin ameliorated influenza viral inflammation in rodents via inhibiting platelet aggregation[J]. Int Immunopharmacol,2020,84:106521
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