Li Tao, Zhao Xiao-Liang, Shen Shuo, DU Mao-Bo, Liu Shu-Zhi
Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences Beijing 100700, China Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2021 Jun;46(11):2728-2736. doi: 10.19540/j.cnki.cjcmm.20210225.302.
On the basis of the qualitative preparation quality markers of Yulian Decoction, we screened out the quantitative markers and explored a general strategy for analyzing the component migration in Chinese herbal pieces, preparations, and plasma. A method capable of simultaneously determining 28 chemical components in Yulian Decoction was established based on HPLC-MS/MS. This method was used to determine the migrated components in herbal pieces-lyophilized powder preparations-rat plasma after administration of Yulian Decoction. Liquid chromatography was performed under the following conditions: C_(18)-reversed phase chromatographic column(2.1 mm × 100 mm, 1.8 μm); acetonitrile-water(containing 0.1% formic acid) as the mobile phase for gradient elution; the flow rate of 0.2 mL·min~(-1). Electrospray ionization source was adopted for mass spectrometry detection, in which positive and negative ion modes and multiple reaction monitoring were applied. Confirmed by the methodological investigation in linear range, recovery(95.48%-103.4%), precision(RSD, 0.45%-3.8%), stability, and repeatability(RSD, 5.6%-14%), the established method was suitable for the detection and quantification of the components in Yulian Decoction. The results showed that in the lyophilized powder of Yulian Decoction, berberine was greater than 5% in mass fraction, magnoflorine, epiberberine, coptisine, palmatine, and limonin in the range of 1%-5%, and dehydroevodiamine, evodiamine, rutaecarpine, costunolide, and dehydrocostus lactone in the range of 0.002%-1%. Of the 28 components detected in pieces, 27 were found to migrate to the lyophilized powder, and 11 were detected in rat plasma. Fifteen components were preliminarily determined as quantitative preparation quality markers for Yulian Decoction, including berberine, epiberberine, coptisine, palmatine, evodiamine, rutaecarpine, limonin, costunolide, dehydrocostus lactone, magnoflorine, jatrorrhizine, columbamine, groenlandicine, chlorogenic acid, and neochlorogenic acid. In conclusion, the HPLC-MS/MS general strategy was established for analyzing the migration of multiple components in Chinese herbal pieces, preparations, and plasma, which can provide the basis for the screening of quantitative preparation quality markers and multi-index quality control of Yulian Decoction.
基于萸连汤定性制备质量标志物,筛选出定量标志物,并探索了一种分析中药饮片、制剂及血浆中成分迁移的通用策略。基于高效液相色谱-串联质谱(HPLC-MS/MS)建立了一种能够同时测定萸连汤中28种化学成分的方法。该方法用于测定萸连汤给药后中药饮片-冻干粉制剂-大鼠血浆中的迁移成分。液相色谱条件如下:C₁₈反相色谱柱(2.1 mm×100 mm,1.8 μm);乙腈-水(含0.1%甲酸)为流动相进行梯度洗脱;流速为0.2 mL·min⁻¹。质谱检测采用电喷雾电离源,其中应用了正、负离子模式及多反应监测。经线性范围、回收率(95.48%-103.4%)、精密度(相对标准偏差,0.45%-3.8%)、稳定性及重复性(相对标准偏差,5.6%-14%)等方法学考察验证,所建立的方法适用于萸连汤中成分的检测和定量。结果表明,萸连汤冻干粉中,小檗碱质量分数大于5%,木兰碱、表小檗碱、黄连碱、巴马汀和柠檬苦素在1%-5%范围内,吴茱萸次碱、吴茱萸碱、吴茱萸果碱、木香烃内酯和去氢木香内酯在0.002%-1%范围内。在饮片检测的28种成分中,27种迁移至冻干粉中,11种在大鼠血浆中被检测到。初步确定15种成分作为萸连汤定量制备质量标志物,包括小檗碱、表小檗碱、黄连碱、巴马汀、吴茱萸碱、吴茱萸果碱、柠檬苦素、木香烃内酯、去氢木香内酯、木兰碱、药根碱、黄连次碱、格陵兰黄连碱、绿原酸和新绿原酸。综上所述,建立了HPLC-MS/MS通用策略用于分析中药饮片、制剂及血浆中多种成分的迁移,可为萸连汤定量制备质量标志物筛选及多指标质量控制提供依据。