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Determination of lipid–water partition coefficient of neutral and ionic drugs by liposome electrokinetic chromatography
Author(s) -
Jiang Hui,
Zhang Hao,
Yin ShiJun,
Lu Min,
Wang Xu,
Yang FengQing
Publication year - 2021
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.202000382
Subject(s) - liposome , partition coefficient , chemistry , chromatography , free energy relationship , ionic strength , analytical chemistry (journal) , aqueous solution , biochemistry , organic chemistry , kinetics , physics , quantum mechanics , reaction rate constant
Profiling of lipid–water partition coefficients ( K L/W ) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid–water partition coefficients (log K L/W ) of neutral and ionic drugs were determined based on an iterative method. The log K L/W values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient ( R 2 = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol–water system, immobilized artificial membrane, Caco‐2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco‐2 cell model, and R 2 was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J – were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log K L/W of drugs.