色谱2017，Vol.35Issue(4)：432-438,7.DOI:10.3724/SP.J.1123.2016.10044
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
Prediction of n-octanol-water partition coefficients of hepatotoxicity/nephrotoxicity components in traditional herbs using quantitative structure-retention relationship models by high performance liquid chromatography
摘要
Abstract
A quantitative structure-retention relationship (QSRR) was proposed to determine n-octanol-water partition coefficients (Kow) of aristolochic acid A, aristolochic acid B, aristololactam and resveratrol in this paper.Sixteen acidic and neutral benzene analogues with reliable experimental Kow data were chosen as model compounds for establishing linear relationship between the apparent n-octanol-water partition coefficient (Kow″) and retention factor of 100% aqueous phase (kw), which corresponds to retention factors of solutes using neat aqueous fraction as mobile phase.Methanol-water mixture was used as mobile phase at various mobile phase pH, and retention time (tR) was rectified by a dual-point retention time correction (DP-RTC).The established models were evaluated by internal and external validations, respectively.QSRR models had good correlation coefficients at different mobile phase pH with correlation coefficients (R2) ranged from 0.980 to 0.987.Both internal (the cross-validated correlation coefficients (R2cv) of 0.982-0.988) and external (0.6%≤relative errors (RE)≤10.9% for all the six verification compounds) validations showed satisfactory results.Kow values of four hepatotoxic/nephrotoxic ingredients in traditional herbs were predicted by QSRR, and compared with the ones obtained by shake-flask method (SFM) and calculated by software as well.The method provided a convenient and rapid way to obtain reliable Kow data.In addition, the proposed protocol realized simultaneous prediction for Kow values of structure-similar components in traditional herbs merely through retention times, thereupon solved the dilemma of Kow measurement by SFM resulting from inaccessibility of separating single component from complex herbs.These Kow data can be applied in toxicity prediction of components in traditional herbs through quantitative structure-activity relationships (QSARs) in a follow-up study.关键词
反相高效液相色谱/摇瓶法/定量结构-保留关系/正辛醇-水分配系数/马兜铃酸/白黎芦醇Key words
reversed-phase high performance liquid chromatography (RP-HPLC)/shake-flask method (SFM)/quantitative structure-retention relationship (QSRR)/n-octanol-water partition coefficients (Kow)/aristolochics/resveratrol分类
化学化工引用本文复制引用
项洋洋,俞慧敏,邓海山,陈静雅,张爱华,池玉梅,韩疏影..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[J].色谱,2017,35(4):432-438,7.基金项目
国家自然科学基金项目(81303311) （81303311）
江苏省自然科学基金项目(BK20130958) （BK20130958）
江苏省属高校自然科学基金项目(13KJB150030) （13KJB150030）
江苏高校优势学科建设工程项目(PAPD) （PAPD）
江苏高校品牌专业建设工程资助项目(PPZY2015A070).National Natural Science Foundation of China (No.81303311) （PPZY2015A070）
Natural Science Foundation of Jiangsu Province (No.BK20130958) （No.BK20130958）
Jiangsu Provincial University Natural Science Foundation (No.13KJB150030) （No.13KJB150030）
Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) （PAPD）
Top-Notch Academic Programs Project of Jiangsu Higher Education Institutions (No.PPZY2015A070). （No.PPZY2015A070）
