Chaotropic salts impact in HPLC approaches for simultaneous analysis of hydrophilic and lipophilic drugs

J Sep Sci. 2021 Aug;44(15):2908-2916. doi: 10.1002/jssc.202100168. Epub 2021 Jun 17.


Simultaneous determination of drugs with different physicochemical properties necessitates thorough research and careful selection of high-performance liquid chromatography conditions. In the present study, various concepts of high-performance liquid chromatography method development for this aim have been discussed. Moreover, the work was motivated by the advantages of utilizing different chaotropic anions as a new promising approach to overcome the limitations of ion-pairing agents commonly used for this purpose. Based on log P values, atorvastatin (log P = 6.36) and lisinopril (log P = -1.22) were chosen as representative examples for lipophilic and hydrophilic drugs, respectively. Several simple, economic, fast, and reliable high-performance liquid chromatography methods were developed for their simultaneous analysis and are presented in a comparative manner, highlighting their advantages and limitations. Peak elution profile showed satisfying retentions and resolution about 3. Photo-diode array calculations were exploited for identifying the molecules by their ultra-violet spectra and peak purity, calculated and presented as rectangular-shaped ratio grams. The linearity check showed excellent results and satisfactory system suitability parameters of both peaks. This confirms the investigation results and conclusions for the influence of the chaotropic salts on N-containing molecules, by increasing their retentivities, and improving peak shapes, even on different quality columns without end-capping and base-deactivating of separation matrixes.

Keywords: atorvastatin; chaotropic anions; dosage form; liquid chromatography; lisinopril.

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Hydrophobic and Hydrophilic Interactions
  • Lipids / chemistry*
  • Pharmaceutical Preparations / analysis*
  • Salts / chemistry


  • Lipids
  • Pharmaceutical Preparations
  • Salts