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止得咳颗粒在大鼠体内的代谢产物研究
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          梁 洁    1, 2, 3, 4* ,郑飘雪 ,陈辉华 ,黄春燕 ,梁炎丽 ,陆春莲 ,谢晶晶 ,马玉明 ,彭嘉文 ,赵立春 ,
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          陈日兰 (1.广西中医药大学药学院,南宁 530200;2.广西高校中药提取纯化与质量分析重点实验室,南宁
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          530200;3.中药固体制剂制造技术国家工程研究中心华南分中心,南宁 530200;4.广西壮瑶药工程技术研究
          中心,南宁 530200;5.钦州市检验检测中心,广西 钦州 535000;6.广西中医药大学附属瑞康医院药剂科,
          南宁 530011)
          中图分类号  R969.1      文献标志码  A      文章编号  1001-0408(2024)02-0172-07
          DOI  10.6039/j.issn.1001-0408.2024.02.09
          摘   要  目的  分析止得咳颗粒在大鼠体内的代谢产物并推测其代谢途径。方法  将雄性SD大鼠随机分为空白组、给药组(止得
          咳颗粒,9.45 g/kg),每组灌胃超纯水或相应药液,每天2次,每次灌胃间隔6~8 h,连续3 d。收集各组大鼠血清、粪便、尿液样品,
          利用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱(UPLC-Q-Exactive-MS)技术鉴定大鼠灌胃止得咳颗粒后上述生物样品中
          的代谢产物,并推测其代谢途径。结果  大鼠灌胃止得咳颗粒后,在其血清、尿液、粪便样品中共鉴定出16个原型成分(如野鸢尾
          黄素、黄芩素、绿原酸等)和11个代谢产物(如山柰酚或木犀草素水合产物、绿原酸甲基化产物、黄芩苷羟基化产物)。其中,血清
          样品中鉴定出8个原型成分和4个代谢产物;尿液样品中鉴定出10个原型成分和7个代谢产物;粪便样品中鉴定出8个原型成分
          和5个代谢产物。结论  止得咳颗粒在大鼠体内的代谢成分主要包括黄芩苷、野鸢尾黄素、绿原酸,主要涉及甲基化、羟基化、葡萄
          糖醛酸化等代谢途径。
          关键词  止得咳颗粒;超高效液相色谱-四极杆-静电场轨道阱高分辨质谱技术;代谢产物;代谢途径;大鼠


          Study on metabolites derived from Zhideke granules in rats in vivo
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          LIANG Jie 1, 2, 3, 4 ,ZHENG Piaoxue ,CHEN Huihua ,HUANG Chunyan ,LIANG Yanli ,LU Chunlian ,XIE
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          Jingjing ,MA Yuming ,PENG Jiawen ,ZHAO Lichun ,CHEN Rilan(1.  School  of  Pharmacy,  Guangxi
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          University  of  Chinese  Medicine,  Nanning  530200,  China;2.  Guangxi  Universities  Laboratory  of  TCM
          Extraction, Purification and Quality Analysis, Nanning 530200, China;3. National Engineering Research Center
          South China Branch of TCM Solid Preparation Manufacturing Technology, Nanning 530200, China;4. Guangxi
          Zhuang Yao Medicine Engineering Technology Research Center, Nanning 530200, China;5. Qinzhou Inspection
          and  Testing  Center,  Qinzhou  535000,  China;6.  Dept.  of  Pharmacy,  Ruikang  Hospital  Affiliated  to  Guangxi
          University of Chinese Medicine, Nanning 530011, China)
          ABSTRACT    OBJECTIVE  To  analyze  the  metabolites  of  Zhideke  granules  and  speculate  its  metabolic  pathway  in  rats  in  vivo.
          METHODS  Male  SD  rats  were  randomly  divided  into  blank  group  and  administration  group (Zhideke  granules,  9.45  g/kg);  they
          were given ultrapure water or relevant medicine, twice a day, every 6-8 h, for 3 consecutive days. Serum, urine and feces samples
          of  rats  were  collected,  and  their  metabolites  were  identified  by  UPLC-Q-Exactive-MS  technique  after  intragastric  administration  of
          Zhideke  granules;  their  metabolic  pathways  were  speculated.  RESULTS  After  intragastric  administration  of  Zhideke  granules,  16
          prototype  components (i.g.  irisflorentin,  baicalin,  chlorogenic  acid)  and  11  metabolites (i.g.  hydration  products  of  kaempferol  or
          luteolin,  methylation  products  of  chlorogenic  acid,  and  hydroxylation  products  of  baicalin)  were  identified  in  serum,  urine  and
          feces of rats. Among them, 8 prototype components and 4 metabolites were identified in serum samples; 10 prototype components
                                                              and  7  metabolites  were  identified  in  urine  samples;  8
              Δ 基金项目 广西创新驱动发展专项(科技重大专项)(No. 桂科
          AA17202046);广西壮族自治区民族药资源与应用工程研究中心项目                 prototype  components  and  5  metabolites  were  identified  in  the
         (No.桂发改高技函〔2020〕2605号);广西中医药重点学科(壮药学)项               fecal  samples.  CONCLUSIONS  The  metabolites  of  Zhideke
          目(No.GZXK-Z-20-64);广西高等学校千名中青年骨干教师培育计划              granules  in  rats  mainly  include  baicalin,  irisflorentin,
          项目(No.桂教人〔2019〕5号);广西中医药大学第三批“歧黄工程”高层               chlorogenic  acid,  and  the  main  metabolic  pathways  included
          次人才团队培育项目                                           methylation, hydroxylation, glucuronidation.
             *第一作者 教授,博士。研究方向:中药药效物质基础与质量控                    KEYWORDS    Zhideke   granules;   UPLC-Q-Exactive-MS;
          制。电话:0771-4953513。E-mail:liangjie1101@126.com
                                                              metabolites; metabolic pathway; rat
              # 通信作者 主任医师,教授。研究方向:中医临床。电话:0771-
          2188309。E-mail:fyhaha@163.com


          · 172 ·    China Pharmacy  2024 Vol. 35  No. 2                               中国药房  2024年第35卷第2期
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