title: Determination of drug lipophilicity by phosphatidylcholine-modified microemulsion high-performance liquid chromatography.
abstract: A new biomembrane-mimetic liquid chromatographic method using a C8 stationary phase and phosphatidylcholine-modified (PC-modified) microemulsion mobile phase was used to estimate unionized and ionized drugs lipophilicity expressed as an n-octanol/water partition coefficient (logP and logD). The introduction of PC into sodium dodecyl sulfate (SDS) microemulsion yielded a good correlation between logk and logD (R(2)=0.8). The optimal composition of the PC-modified microemulsion liquid chromatography (PC-modified MELC) mobile phase was 0.2% PC-3.0% SDS-6.0% n-butanol-0.8% ethyl acetate-90.0% water (pH 7.0) for neutral and ionized molecules. The interactions between the analytes and system described by this chromatographic method is more similar to biological membrane than the n-octanol/water partition system. The result in this paper suggests that PC-modified MELC can serve as a possible alternative to the shake-flask method for high-throughput unionized and ionized drugs lipophilicity determination and simulation of biological processes.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Xuan
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Xu
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 Pharmaceutics, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: godck01@163.com.
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; D020003:1-Octanol / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004655:Emulsions / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D014867:Water; D012967:Sodium Dodecyl Sulfate; D020001:1-Butanol; D020003:1-Octanol
keywords: 1-Butanol (PubChem CID: 263); 1-Octanol (PubChem CID: 957); Biomembrane-mimetic liquid chromatography; Ethyl acetate (PubChem CID: 8857); Lipophilicity logP/logD; Phosphatidylcholine (PubChem CID: 45266626); Phosphatidylcholine-modified microemulsion; Principal component analysis; Sodium dodecyl sulfate (SDS) (PubChem CID: 3423265)