硅胶基质固定相离子对反相液相色谱法测定强离解化合物的正辛醇/水分配系数  

Prediction of n-octanol/water partition coefficient of strongly ionized compounds by ion-pair reversed-phase liquid chromatography with silica-based stationary phase

作　　者：刘小兰 高薇 梁超 乔俊琴[1] 王康 练鸿振[1] LIU Xiaolan;GAO Wei;LIANG Chao;QIAO Junqin;WANG Kang;LIAN Hongzhen(State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry & Chemical Engineering and Center of Materials Analysis, Nanjing University, Nanjing 210023, China;Jumpcan Pharmaceutical Group Co., Ltd., Taixing 225441, China)

机构地区：[1]生命分析化学国家重点实验室,南京大学化学化工学院,南京大学现代分析中心,江苏南京210023 [2]济川药业集团有限公司,江苏泰兴225441

出　　处：《色谱》2021年第11期1230-1238,共9页Chinese Journal of Chromatography

基　　金：国家自然科学基金(21577057,91643105,21874065);江苏省自然科学基金(BK20171335).

摘　　要：反相液相色谱(RPLC)是测定正辛醇/水分配系数(log P)的有效方法,但由于缺少同类型模型化合物,RPLC在测定强离解化合物的log P时遇到挑战。该文在硅胶基质C18色谱柱上,采用离子抑制反相液相色谱(IS-RPLC)和离子对反相液相色谱(IP-RPLC)分别对中性化合物、酚酸、羧酸、磺酸及部分两性化合物的保留行为进行了系统研究。在IS-RPLC模式下,利用中性化合物、弱离解的酚酸和苯羧酸作为模型化合物,建立了表观正辛醇/水分配系数(log D)与纯水相保留因子对数值(log kw)的定量结构-保留行为关系(QSRR)模型,测定了19种离解化合物的log D值,作为后续IP-RPLC的模型化合物及验证化合物。在IP-RPLC模式下,将中性、弱离解和强离解化合物作为混合模型组,以溶质静电荷ne、氢键酸碱性参数A和B为桥梁,建立了线性良好的log D-log kw-IP模型,采用3种不同类型的离解化合物进行了外部验证实验,预测值误差低于10%,证实了模型的可靠性。在此基础上,预测了8种强离解化合物的log D7.0值(pH 7.0条件下的log D值)。研究表明,利用结构相关参数沟通不同类型的模型化合物,是实现IP-RPLC测定强离解化合物log D值的一种行之有效的方法。与聚乙烯醇基质色谱柱相比,通用型的硅胶基质色谱柱上尽管存在着更多的次级作用,但可以为强离解化合物log D的测定提供更灵活的选择。The n-octanol/water partition coefficient(log P)is an important parameter to characterize the overall hydrophobicity of organic compounds.Reversed-phase liquid chromatography(RPLC)has been recommended as an effective method for the indirect determination of log P by the Organization for Economic Cooperation and Development(OECD).Using RPLC,most studies focus on the determination of log P or the apparent n-octanol/water partition coefficient(log D)of neutral compounds and weakly ionized compounds.However,the experimental log P or log D values of strongly ionized compounds have rarely been reported.In our previous work,the experimental log D of strongly ionized compounds could be determined well by ion-pair reversed-phase liquid chromatography(IP-RPLC)on an octadecyl-poly(vinyl alcohol)column using the log D-log kw-IP model established by different types of model compounds.However,the universality of this strategy for different chromatographic columns has yet to be verified.In this study,the retention behavior of neutral compounds,phenolic acids,carboxylic acids,sulfonic acids,and some amphoteric compounds was systematically investigated on a silica-based C18 column(150 mm×4.6 mm,5μm)via ion-suppressed RPLC(IS-RPLC)and IP-RPLC,respectively.In the IS-RPLC mode,methanol and 20 mmol/L ammonium dihydrogen phosphate buffer(pH 7.0)were used as the mobile phase to perform isocratic elution at different methanol ratios.The log kw values of the test compounds were obtained using the linear solvent strength(LSS)model.Neutral compounds,weakly ionized phenolic acids and benzene carboxylic acids were then used as model compounds to establish the log D-log kw-IS model.The quantitative structure-retention relationship(QSRR)model,including structure-related descriptors like the charge(ne)and Abraham solvation parameters(A and B),exhibited much better correlation than the unary linear regression model between log D and log kw-IS.The log D7.0(log D under pH 7.0)values of 19 ionized compounds were then determined by the model;the d

关 键 词：离子对反相液相色谱 强离解化合物 正辛醇/水分配系数 定量结构-保留行为关系 硅胶基质色谱柱 

分 类 号：O658[理学—分析化学]