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.
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).
Copyright © 2015 Elsevier B.V. All rights reserved.