目的 研究印烏堿在砂炒（油浴模擬）過程中的結(jié)構(gòu)轉(zhuǎn)化途徑并比較印烏堿及其轉(zhuǎn)化產(chǎn)物的毒性。方法 采用HPLC法篩選出印烏堿發(fā)生結(jié)構(gòu)轉(zhuǎn)化的溫度和時(shí)間參數(shù)；通過柱色譜法和NMR、MS等波譜法，分離、鑒定出印烏堿的砂炒轉(zhuǎn)化產(chǎn)物；采用心臟毒性實(shí)驗(yàn)比較原型成分印烏堿及其轉(zhuǎn)化產(chǎn)物的毒性。結(jié)果 通過比較不同炮制溫度、時(shí)間樣品的HPLC色譜圖，篩選出印烏堿在160～180℃，加熱10～30 min時(shí)發(fā)生結(jié)構(gòu)轉(zhuǎn)化；分離、鑒定出砂炒產(chǎn)物mithaconitine；II導(dǎo)聯(lián)心電圖（electrocardiogram，ECG）表明，0.06 mg/kg印烏堿可引起正常大鼠出現(xiàn)室性早搏（ventricular premature beat，VPB）、室性心動(dòng)過速（ventricular tachyrhythmia，VT）等心律失?，F(xiàn)象；mithaconitine在該劑量下未引起大鼠典型的心律失常ECG。結(jié)論 砂炒過程中，印烏堿的C-8位脫去乙酰基，轉(zhuǎn)化為14-benzoylpseudaconine；接著，14-benzoylpseudaconine的C-8位、C-15位發(fā)生脫水反應(yīng)轉(zhuǎn)化為mithaconitine，達(dá)到砂炒減毒的目的。

Objective To study the structural transformation pathway of indaconitine in stir-frying with sand process and compare the toxicity of indaconitine with its processing products. Methods Using high performance liquid chromatography to screen out the temperature and time parameters of the structural transformation of indaconitine. The processing products were separated by column chromatography and identified by NMR and MS. The cardiotoxicity test was chosen to compare the toxicity of indaconitine with its processing products. Results Indaconitine was converted into mithaconitine when it was heated at 160-180℃ for 10-30 min. With a dose of 0.06 mg/kg, indaconitine could induce ventricular arrhythmia in rats, such as ventricular premature beat, ventricular tachycardia. However, mithaconitine had no arrhythmogenic effect at the same dosage. Conclusion The structural transformation pathway of indaconitine has been defined:deacetylating at C-8 position, generating 14-benzoylpseudaconine, and converting benzoylpseudaconine into mithaconitine by dehydration reaction at C-8 and C-15 position. Compared with indaconitine, the toxicity of mithaconitine was reduced.

R283.1

國家自然科學(xué)基金資助項(xiàng)目（81403104）；高等學(xué)校博士學(xué)科點(diǎn)專項(xiàng)科研基金資助課題（新教師類）（20135132120011）；四川省科技廳省級(jí)科技計(jì)劃項(xiàng)目（20YYJC0970）；成都中醫(yī)藥大學(xué)“杏林學(xué)者”學(xué)科人才科研提升計(jì)劃（030041070）