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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