目的 采用超高效液相色譜-四極桿-飛行時(shí)間質(zhì)譜法（UPLC-Q-TOF-MS/MS）分析鑒定大鼠ig給藥白術(shù)后血清、尿液/糞便和組織中的原型成分及代謝產(chǎn)物，研究白術(shù)化學(xué)成分在大鼠體內(nèi)的分布差異，并推測(cè)其代謝途徑。方法 SD健康大鼠27只，按照人體等效劑量的2倍高倍劑量ig給予白術(shù)水煎液，制備給藥后大鼠血清、尿液/糞便和組織（腸、肝、腎、脾、心、腦）的甲醇提取液，采用電噴霧離子源（ESI）正、負(fù)離子模式下檢測(cè)。根據(jù)實(shí)驗(yàn)得到的化合物相對(duì)保留時(shí)間、質(zhì)荷比、準(zhǔn)分子離子峰及特征碎片離子等信息，與對(duì)照品、文獻(xiàn)數(shù)據(jù)、MassBank Europe數(shù)據(jù)庫(kù)、MassBank of North America數(shù)據(jù)庫(kù)以及安捷倫個(gè)人化合物數(shù)據(jù)庫(kù)與譜庫(kù)（PCDL）進(jìn)行比較，鑒定白術(shù)在大鼠體內(nèi)的原型成分代謝產(chǎn)物與代謝產(chǎn)物，推測(cè)其代謝途徑。結(jié)果 基于UPLC-Q-TOF-MS/MS技術(shù)結(jié)合本課題組前期對(duì)白術(shù)藥材成分定性分析結(jié)果，大鼠血清中共鑒定出原型成分53個(gè)、代謝型成分54個(gè)；大鼠尿液中共鑒定出原型成分56個(gè)、代謝型成分48個(gè)；大鼠糞便中共鑒定出原型成分90個(gè)、代謝型成分53個(gè)；大鼠各組織中共鑒定出原型成分62個(gè)、代謝型成分54個(gè)。原型成分主要涉及酚酸類、萜類、有機(jī)酸類等；代謝型成分主要來(lái)自酚酸類、萜類等。其中，在腸、肝、腎、脾等組織中富集的原型成分主要以萜類物質(zhì)為主。結(jié)論 建立的UPLC-Q-TOF-MS/MS分析方法能有效鑒別白術(shù)在大鼠體內(nèi)的原型及代謝型成分群。白術(shù)在大鼠體內(nèi)主要進(jìn)行Ⅰ相和Ⅱ相代謝反應(yīng)。其中，綠原酸類成分在大鼠體內(nèi)代謝較快，生成多種酚酸類物質(zhì)，且其代謝產(chǎn)物主要通過(guò)腎臟排泄。而萜類成分在大鼠體內(nèi)多以原型形式存在，代謝較為緩慢，且在腸、肝、腎、脾等組織中顯著富集，結(jié)合相關(guān)報(bào)道的白術(shù)健脾、補(bǔ)氣、保肝的藥理作用，推測(cè)萜類成分是白術(shù)潛在的藥效物質(zhì)基礎(chǔ)。

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

中國(guó)中醫(yī)科學(xué)院科技創(chuàng)新工程項(xiàng)目（CI2023E002-05）；廣西科技重大專項(xiàng)（桂科AA22096029-3；桂科AA23023035-4）；湖北省中醫(yī)藥重點(diǎn)學(xué)科建設(shè)項(xiàng)目（鄂中醫(yī)通[2023]2號(hào)）；湖北省自然科學(xué)基金項(xiàng)目（2023AFD146）；國(guó)家自然科學(xué)基金項(xiàng)目（82004253）