天芪降糖胶囊（TQ）由黄芪、天花粉等十味中药组成，主要用于2型糖尿病早期及并发症的干预治疗。我们前期对其进行临床基因芯片研究表明，药物代谢酶硫代嘌呤甲基转移酶（TPMT）与该药抗糖尿病作用有关。TPMT是一种催化硫嘌啉类化合物甲基化的酶，参与硫嘌啉类药物的体内代谢，TPMT的活性与这类药物的临床疗效和毒性密切相关。但目前尚无TPMT与中药成分代谢及糖尿病机制研究的相关报道。本项目拟建立快速筛选和识别复杂体系中TPMT酶亲和活性成分的联用新技术：HPLC-TPMT EAD-MS，对天芪降糖胶囊的体内体外活性成分进行靶向筛选及分析，并采用HSCCC导向制备该类化合物。建立一套基于HPLC-TPMT EAD-MS/HSCCC技术的中药复方中TPMT酶亲和底物的快速筛选和制备方法，并应用现代光谱学和化学方法鉴定活性成分结构。建立基于靶标活性成分及体内代谢物的快速筛选、适合中药复杂成分的研究方法。

Tianqi Jiangtang (TQ) capsule, a traditional Chinese medicine (TCM) preparation containing ten herbal medicines, has been commonly utilized for early type 2 diabetes and its complications treatment in China. Our previous work indicated that the thiopurine S-methyltransferase (TPMT) gene was significantly associated with the anti-diabetic effect of the drug. TPMT is an enzyme that catalyzes S-methylation of thiopurine drugs. TPMT activity is associated with the clinical efficacy and excessive toxicity of these drugs. However, there is no relevant report about TPMT, metabolism of traditional Chinese medicines (TCMs) and diabetes mechanism research. In the present study, a new HPLC-TPMT EAD-MS hyphenated technique will be established for rapid screening and identification of TPMT substrates in order to quickly define the active constituents in TQ capsule. HSCCC will be applied for separation of the active constituents of TQ capsule. A quickly screening and preparation method will be developed for TPMT substrates in TCM prescription based on HPLC-TPMT EAD-MS/HSCCC. Modern spectroscopy and chemical method will also be used to identify the structure of the active compounds. Establishing a rapid screening and analyzing approach for complex material base research of TCM basing on targeted bioactive compounds and metabolite analysis.