目的 采用超高效液相色谱-四极杆-飞行时间质谱法（UPLC-Q-TOF-MS/MS）分析鉴定大鼠ig给药白术后血清、尿液/粪便和组织中的原型成分及代谢产物，研究白术化学成分在大鼠体内的分布差异，并推测其代谢途径。方法 SD健康大鼠27只，按照人体等效剂量的2倍高倍剂量ig给予白术水煎液，制备给药后大鼠血清、尿液/粪便和组织（肠、肝、肾、脾、心、脑）的甲醇提取液，采用电喷雾离子源（ESI）正、负离子模式下检测。根据实验得到的化合物相对保留时间、质荷比、准分子离子峰及特征碎片离子等信息，与对照品、文献数据、MassBank Europe数据库、MassBank of North America数据库以及安捷伦个人化合物数据库与谱库（PCDL）进行比较，鉴定白术在大鼠体内的原型成分代谢产物与代谢产物，推测其代谢途径。结果 基于UPLC-Q-TOF-MS/MS技术结合本课题组前期对白术药材成分定性分析结果，大鼠血清中共鉴定出原型成分53个、代谢型成分54个；大鼠尿液中共鉴定出原型成分56个、代谢型成分48个；大鼠粪便中共鉴定出原型成分90个、代谢型成分53个；大鼠各组织中共鉴定出原型成分62个、代谢型成分54个。原型成分主要涉及酚酸类、萜类、有机酸类等；代谢型成分主要来自酚酸类、萜类等。其中，在肠、肝、肾、脾等组织中富集的原型成分主要以萜类物质为主。结论 建立的UPLC-Q-TOF-MS/MS分析方法能有效鉴别白术在大鼠体内的原型及代谢型成分群。白术在大鼠体内主要进行Ⅰ相和Ⅱ相代谢反应。其中，绿原酸类成分在大鼠体内代谢较快，生成多种酚酸类物质，且其代谢产物主要通过肾脏排泄。而萜类成分在大鼠体内多以原型形式存在，代谢较为缓慢，且在肠、肝、肾、脾等组织中显著富集，结合相关报道的白术健脾、补气、保肝的药理作用，推测萜类成分是白术潜在的药效物质基础。

Objective Ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to analyze and identify the prototypical components and metabolites in serum, urine/feces, and tissues of Atractylodes macrocephala in rats after gavage administration of A. macrocephala to study the differences in the distribution of A. macrocephala 's chemical constituents in the body of the rats and speculate on their metabolic pathways. Methods A total of 27 SD healthy rats were given the decoction of A. macrocephala by gavage at two times the high human equivalent dose, methanol extracts of serum, urine/feces and tissues (heart, liver, spleen, kidney, intestine and brain) of the administered rats were prepared and assayed using electrospray ionization source (ESI) in positive and negative ion mode. Based on the information obtained on relative retention time, mass-to-charge ratio, quasi-molecular ion peaks and characteristic fragment ions of the compounds, the prototypes of A. macrocephala in rats were identified by comparing them with the standards, literature data, the MassBank Europe database, the MassBank of North America database, and the Agilent Personal Compound Database and Spectral Library (PCDL) constituent metabolites and metabolites, and speculate on the metabolic pathways. Results Based on the UPLC-Q-TOF-MS/MS technology and combined with the results of the preliminary qualitative analysis of the components of A. macrocephala. medicinal materials in this experiment, a total of 53 prototypical and 54 metabolic components were identified in rat serum, 56 prototypical and 48 metabolic components in rat urine, 90 prototypical and 53 metabolic components in rat feces, 62 prototypical components and 54 metabolic components in rat tissues. The prototypical components were mainly related to phenolic acids, terpenoids and organic acids; the metabolizable components were mainly from phenolic acids and terpenoids, etc. The metabolizable components were mainly from phenolic acids and terpenoids. Among them, the prototype components enriched in tissues such as the intestine, liver, kidney, and spleen are mainly terpenoids. Conclusion The UPLC-Q-TOF-MS/MS analytical method established in this study can effectively identify the prototype and metabolite component groups of Atractylodes macrocephala in rats. A. macrocephala mainly undergoes Phase I and Phase II metabolic reactions in rats. Among them, chlorogenic acid components are metabolized relatively quickly in rats, generating a variety of phenolic acid substances, and their metabolites are mainly excreted through the kidneys. Terpenoid components, on the other hand, mostly exist in the form of prototypes in rats, are metabolized relatively slowly, and are significantly enriched in tissues such as the intestine, liver, kidney, and spleen. Combining with the reported pharmacological effects of A. macrocephala, such as invigorating the spleen, replenishing qi, and protecting the liver, it is speculated that terpenoid components are the potential material basis for the pharmacological effects of A. macrocephala.

R284.1

中国中医科学院科技创新工程项目（CI2023E002-05）；广西科技重大专项（桂科AA22096029-3；桂科AA23023035-4）；湖北省中医药重点学科建设项目（鄂中医通[2023]2号）；湖北省自然科学基金项目（2023AFD146）；国家自然科学基金项目（82004253）