HPLC stability-indicating method approach

To meet the speed and high efficiencies in separations demanded by the pharmaceutical industry, combined HPLC methods have been frequently used to simultaneously determine combination products [67]. A stability-indicating method for the simultaneous determination of aspirin and warfarin in warfarin sodium/aspirin combination tablets has been recently developed and validated [68]. In another example [69], the simultaneous determination of enalapril (2) and its two degradants, enapril-DKP (3) and enalapril-diacid (4), and felodipine (5) and its degradant, named HI52/37 (6) was achieved using combined method approach. 

Thus, a comparison between HPLC-derived lipophilicity indices and calculated log P values for a series of 8-substituted xanthines showed a clear influence of conformational effects. 8 In this case, Rekker s method was unable to take 3D effects into account, but the difference between experimental and predicted values was structure dependent rather than constant. Conformational analyses confirmed that a smaller than predicted lipophilicity was associated with folded conformers stabilized by hydrophobic and van der Waals forces and having part of their nonpolar surface masked from the aqueous phase. A 4D theoretical approach (log P calculations by MLP for conformers generated by high temperature molecular dynamics) suggests that these effects should be lower in an w-octanol/water system than in RP-HPLC. Indeed, the n-octanol/water system is not the most suitable model to study intramolecular interactions in nonpolar media because a surprisingly high proportion of water is dissolved in the w-octanol. Recall, however, that w-octanol, despite some limitations, was selected by many workers in the field as a model for biological membranes. 

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