title: Establishment of quantitative retention-activity model by optimized microemulsion liquid chromatography.
abstract: The effective permeability coefficient is of theoretical and practical importance in evaluation of the bioavailability of drug candidates. However, most methods currently used to measure this coefficient are expensive and time-consuming. In this paper, we addressed these problems by proposing a new measurement method which is based on the microemulsion liquid chromatography. First, the parallel artificial membrane permeability assays model was used to determine the effective permeability of drug so that quantitative retention-activity relationships could be established, which were used to optimize the microemulsion liquid chromatography. The most effective microemulsion system used a mobile phase of 6.0% (w/w) Brij35, 6.6% (w/w) butanol, 0.8% (w/w) octanol, and 86.6% (w/w) phosphate buffer (pH 7.4). Next, support vector machine and back-propagation neural networks are employed to develop a quantitative retention-activity relationships model associated with the optimal microemulsion system, and used to improve the prediction ability. Finally, an adequate correlation between experimental value and predicted value is computed to verify the performance of the optimal model. The results indicate that the microemulsion liquid chromatography can serve as a possible alternative to the PAMPA method for determination of high-throughput permeability and simulation of biological processes.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China; School of Management Engineering, Hua Xia Technical College, Guangzhou, 510935, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Analytical Chemistry, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Haoshi
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
authors.forename: Liangxing
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
authors.forename: Yinnong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
authors.forename: Liuyun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
authors.forename: Chongkai
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: 13724117338@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D020001:1-Butanol / Q000737:chemistry; D001682:Biological Availability; D002853:Chromatography, Liquid; D008956:Models, Chemical; D000442:Octanols / Q000737:chemistry; D010539:Permeability
chemical_list: D000442:Octanols; D020001:1-Butanol
keywords: Artificial membrane，QRAR model; Chromatography; Microemulsion; Permeability