Application of the ion pair concept to the n-octanol-water partitioning of cefepime and cefpirome.
The ion pair concept was applied for the assessment of lipophilicity of cefepime and cefpirome. Octanol-water distribution coefficients were determined in presence of different concentrations [X-] of sodium octanesulphonate. The log Dx values within the linear part of the log Dx/[X-] relationships were extrapolated to log Do values corresponding to the partitioning in absence of the counter ion. Measurements were feasible at pH values close to the isoelectric points of the acidic and basic functions. In that pH range the conduction of the experiments in presence of the hydrophobic counter anion facilitated the partitioning of the two cephalosporins to octanol, circumventing the problems arising from their high hydrophilicity. This procedure could not be applied at lower pH, possibly due to a further drastic decrease in the 'intrinsic' lipophilicity or to reduced ion pairing potential of octanesulphonate, and at higher pH due to the disruption of the zwitterionic structure. Extrapolated log Do values were compared to actual log D measurements performed for a reference quinolinium compound and for cefpirome. Extrapolated retention factors log kw close to the isoelectric point were also determined by reversed phase HPLC and compared to the log Do values.
Koufopoulou
S-A
SA
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 157 71, Greece.
Pistos
C
C
Giaginis
C
C
Tsantili-Kakoulidou
A
A
D020003:1-Octanol / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000077723:Cefepime; D002511:Cephalosporins / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008956:Models, Chemical; D015394:Molecular Structure; D014867:Water / Q000737:chemistry*; D000097572:Cefpirome
D020003:1-Octanol; D000900:Anti-Bacterial Agents; D000077723:Cefepime; D002511:Cephalosporins; D007477:Ions; D014867:Water; D000097572:Cefpirome