分析化学2016，Vol.44Issue(6)：958-964,7.DOI:10.11895/j.issn.0253-3820.150997
基于反相高效液相色谱法构建 QSRR 模型测定萘类及蒽醌类化合物的正辛醇-水分配系数
Determination of n-Octanol/Water Partition Coefficients of Naphthalenes and Anthraquinones Using Quantitative Structure-Retention Relationship Models by Reversed Phase-High Performance Liquid Chromatography
摘要
Abstract
n-Octanol/ water partition coefficients (Kow ) is an important parameter commonly used to explain toxicity, activity and transmembrane of drugs. However, it is difficult to be detected by direct experimental determination. In this work, a set of 29 neutral and acidic analogues of naphthalene and anthraquinone with reliable experimental Kow data was chosen as model compounds for establishing linear relationship between the logarithm of apparent n-octanol/ water partition coefficient (lgKow"), and the logarithm of reversed phase-high performance liquid chromatography (RP-HPLC) retention factor of the solutes corresponding to neat aqueous fraction of mobile phase (lgkw ) as the quantitative structure-retention relationship (QSRR) model. Methanol-water mixture was used as mobile phase at various pH, and retention time (tR ) was rectified by a dual-point retention time correction (DP-RTC) in this method. The experiment results indicated that the proposed QSRR model had good correlation coefficient R2 = 0. 974 -0. 976 with satisfactory results of internal and external validation (the cross-validated correlation coefficient R2cv of 0. 970-0. 973, and 1. 4% ≤relative error (RE)≤7. 9% for all the 6 verification compounds). In addition, this QSRR model was compared with linear solvation energy relationship ( LSER) involved in different descriptors of molecular structure, showing no differences. The QSRR model was applied to measure Kow of 11 naphthalenes and anthraquinones, and the predicted data were compared with Shake-flask method (SFM) experimental ones, as well as calculated ones obtained by software. The results suggested that the proposed method for Kow determination in this work was more accurate, simple and fast. To the best of our knowledge, this is the first report on measuring Kow data for these compounds. The proposed strategy provides the possibility in determining Kow of lipophilic components in complex mixture more quickly and accurately by RP-HPLC.关键词
正辛醇-水分配系数/表观正辛醇-水分配系数/反相高效液相色谱/QSRR 模型/摇瓶法/萘类和蒽醌类化合物Key words
n-Octanol/ water partition coefficients/Apparent n-octanol/ water partition coefficients/Reversed-phase high performance liquid chromatography/Quantitative structure-retention relationship model/Shake-flask method/Naphthalenes and anthraquinones引用本文复制引用
俞慧敏,韩疏影,邓海山,池玉梅..基于反相高效液相色谱法构建 QSRR 模型测定萘类及蒽醌类化合物的正辛醇-水分配系数[J].分析化学,2016,44(6):958-964,7.基金项目
本文系国家自然科学基金( No.81303311)、江苏省自然科学基金( No. BK20130958)、江苏省属高校自然科学基金(No.13KJB150030)、江苏高校优势学科建设工程资助项目(PAPD)资助This work was supported by the National Natural Science Foundation of China (No.81303311), the Natural Science Foundation of Jiangsu, China (No. BK20130958), the Natural Science Foundation for Colleges of Jiangsu Province ( No.13KJB150030), and the Priority Academic Program Development of Jiangsu Higher Education Institutions （ No.81303311）
