高效液相色谱法构建定量结构-保留关系预测中药肝肾毒性组分的正辛醇-水分配系数值

发布时间：2018-04-04 18:54

  本文选题：反相高效液相色谱　切入点：摇瓶法　出处：《色谱》2017年04期

【摘要】：构建了定量结构-保留关系(QSRR)测定马兜铃酸A、马兜铃酸B、马兜铃内酰胺及白黎芦醇的正辛醇-水分配系数(K_(ow))。采用反相高效液相色谱(RP-HPLC)法,以甲醇-水为流动相,以16种已知K_(ow)值的酸性和中性苯系物为模型化合物,以保留时间两点校正法(DP-RTC)校正保留时间,并由Snyder-Soczewinski方程得100%水相保留因子k_w,建立了表观正辛醇-水分配系数K_(ow)″与k_w的定量关系(QSRR模型),并对模型进行了内、外部验证。结果显示,不同pH下的QSRR模型线性相关性良好(相关系数R~2为0.980~0.987),内部验证(交叉验证相关系数R_(cv)~2为0.982~0.988)和外部验证结果(6种验证化合物的相对误差RE为0.6%~10.9%)令人满意。将建立的QSRR模型应用于中药中4种潜在肝肾毒性化合物的K_(ow)测定,并与软件计算值、摇瓶法(SFM)实验值比较,结果显示该方法准确性更高,且简单快捷。该文提出的采用中性及酸性苯系物建立QSRR模型,通过对结构与性质相似的中药材组分进行RP-HPLC分析,得到各待测组分的保留时间即可获得其K_(ow)值的简便策略,解决了中药组分复杂且难以分离、无法通过SFM测定其K_(ow)值的问题,为通过定量-构效关系(QSAR)模型实现快速预测中药组分的肝肾毒性提供了可靠的K_(ow)数据。
[Abstract]:A quantitative structure-retention relationship (QSRR) was established for the determination of aristolochic acid A, aristolochic acid B, aristolocholactam and aristolochin.The RP-HPLC method was used to correct the retention time with methanol-water as mobile phase and 16 acidic and neutral benzenes with known KW values as model compounds. The retention time was corrected by two-point retention time correction method.The QSRR model of the apparent n-octanol-water partition coefficient K _ S _ w "and KW / KW was established from the Snyder-Soczewinski equation, and the internal and external verification of the model was also carried out. The model was obtained by using the Snyder-Soczewinski equation as the retention factor of 100% water phase, and the quantitative relationship between the apparent n-octanol-water partition coefficient (KW) and KW was established.The results showed that the linear correlation of the QSRR model at different pH was satisfactory (the correlation coefficient Rn2 was 0.980 ~ 0.987m, the internal validation coefficient was 0.998 ~ (2) R_(cv)~2 = 0.988) and the relative error RE of the six kinds of validation compounds was 0.6 ~ (10.9).The established QSRR model was applied to the determination of four potential hepatorenal toxic compounds in traditional Chinese medicine, and compared with the calculated value of software and the experimental value of shaking flask method, the results showed that the method was more accurate and simple and rapid.In this paper, the QSRR model was established by neutral and acidic benzene series. By RP-HPLC analysis of the components of Chinese medicinal materials with similar structure and property, the simple strategy of obtaining the value of QSRR by the retention time of each component was obtained.The problem that the components of traditional Chinese medicine are complex and difficult to separate can not be measured by SFM. It provides reliable data for rapid prediction of liver and kidney toxicity of traditional Chinese medicine components by quantitative structure-activity relationship (QSAR) model.
【作者单位】： 南京中医药大学;
【基金】：国家自然科学基金项目(81303311) 江苏省自然科学基金项目(BK20130958) 江苏省属高校自然科学基金项目(13KJB150030) 江苏高校优势学科建设工程项目(PAPD) 江苏高校品牌专业建设工程资助项目(PPZY2015A070)~~
【分类号】：O657.72;R285.1
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本文编号：1711256