Determination of drug lipophilicity by phosphatidylcholine-modified microemulsion high-performance liquid chromatography

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 (R2 = 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.

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