title: The development of a high-throughput measurement method of octanol/water distribution coefficient based on hollow fiber membrane solvent microextraction technique.
abstract: This paper describes the development of a novel high-throughput hollow fiber membrane solvent microextraction technique for the simultaneous measurement of the octanol/water distribution coefficient (logD) for organic compounds such as drugs. The method is based on a designed system, which consists of a 96-well plate modified with 96 hollow fiber membrane tubes and a matching lid with 96 center holes and 96 side holes distributing in 96 grids. Each center hole was glued with a sealed on one end hollow fiber membrane tube, which is used to separate the aqueous phase from the octanol phase. A needle, such as microsyringe or automatic sampler, can be directly inserted into the membrane tube to deposit octanol as the accepted phase or take out the mixture of the octanol and the drug. Each side hole is filled with aqueous phase and could freely take in/out solvent as the donor phase from the outside of the hollow fiber membranes. The logD can be calculated by measuring the drug concentration in each phase after extraction equilibrium. After a comprehensive comparison, the polytetrafluoroethylene hollow fiber with the thickness of 210 μm, an extraction time of 300 min, a temperature of 25 °C and atmospheric pressure without stirring are selected for the high throughput measurement. The correlation coefficient of the linear fit of the logD values of five drugs determined by our system to reference values is 0.9954, showed a nice accurate. The -8.9% intra-day and -4.4% inter-day precision of logD for metronidazole indicates a good precision. In addition, the logD values of eight drugs were simultaneously and successfully measured, which indicated that the 96 throughput measure method of logD value was accurate, precise, reliable and useful for high throughput screening.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
authors.forename: James J
authors.initials: JJ
authors.lastname: Bao
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China. Electronic address: lyx@tju.edu.cn.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D057166:High-Throughput Screening Assays; D016014:Linear Models; D059627:Liquid Phase Microextraction / Q000379:methods*; D008567:Membranes, Artificial; D000442:Octanols / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D015203:Reproducibility of Results; D014867:Water / Q000737:chemistry*
chemical_list: D008567:Membranes, Artificial; D000442:Octanols; D004364:Pharmaceutical Preparations; D014867:Water
keywords: Drug screening; High-throughput; Hollow fiber membrane; Octanol/water distribution coefficient; Solvent microextraction