Retention of quinolones on human serum albumin and α₁-acid glycoprotein HPLC columns: Relationships with different scales of lipophilicity

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• 作者：Francesco Barbato ; Giuseppina di Martino ; Lucia Grumetto ; Maria Immacolata La Rotonda
• 关键词：Quinolones ; Human serum albumin ; α ; ₁-Acid glycoprotein ; Biochromatography ; Lipophilicity
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2007
• 出版时间：March 2007
• 年：2007
• 卷：30
• 期：3-4
• 页码：211-219
• 全文大小：636 K

文摘

The retention of 10 quinolone antibacterial agents on HPLC stationary phases supporting human serum albumin (HSA) or α₁-acid glycoprotein (AGP) was investigated. Among ofloxacine and flumequine, the two chiral compounds in the selected set, only the latter showed a split chromatographic peak and only on HSA but not on AGP, indicating that enantioselective specific sites play only a minor role in the retention. The retention of quinolones, which included four acidic and six zwitterionic congeners, was correlated with various lipophilicity scales: (i) theoretically calculated values, c log P, (ii) values measured at pH 7.4 by the shake-flask method, log D^7.4, and (iii) values extrapolated by retention data measured by ion-pair reversed-phase high performance liquid chromatography (RP-HPLC). We assumed that the latter values, log P_i.p., were close to the lipophilicity of the neutral forms, log P^N, for both acidic and zwitterionic congeners. No relationship was found between retention on serum proteins and c log P values, whereas a reasonable relationship was found with log D^7.4 values, but only when the two subclasses, acidic and zwitterionic congeners, were considered separately. The relationship between retention data on serum proteins and log P_i.p. values indicated that the affinity for serum proteins depends on the lipophilicity of the neutral forms only for log P values up to 1.5. Above this value, protein retention does not further increase, becoming almost constant. Based on both the observations above reported and the small values of the slopes of regression equations, we conclude that the interaction of the more lipophilic quinolones, mainly the zwitterions, with serum proteins is not governed uniquely by lipophilicity but also by other mechanisms, probably of electrostatic nature.