Background: Significant advances have been occurred in analytical research since the 1970s
by Liquid Chromatography (LC) as the separation method. Reverse Phase Liquid Chromatography
(RPLC) method, using hydrophobic stationary phases and polar mobile phases, is the most commonly
used chromatographic method. However, it is difficult to analyze some polar compounds with this
method. Another separation method is the Normal Phase Liquid Chromatography (NPLC), which involves
polar stationary phases with organic eluents. NPLC presents low-efficiency separations and
asymmetric chromatographic peak shapes when analyzing polar compounds. Hydrophilic Interaction
Liquid Chromatography (HILIC) is an interesting and promising alternative method for the analysis of
polar compounds. HILIC is defined as a separation method that combines stationary phases used in the
NPLC method and mobile phases used in the RPLC method. HILIC can be successfully applied to all
types of liquid chromatographic separations such as pharmaceutical compounds, small molecules, metabolites,
drugs of abuse, carbohydrates, toxins, oligosaccharides, peptides, amino acids and proteins.
Objective: This paper provides a general overview of the recent application of HILIC in the pharmaceutical
research in the different sample matrices such as pharmaceutical dosage form, plasma, serum,
environmental samples, animal origin samples, plant origin samples, etc. Also, this review focuses on
the most recent and selected papers in the drug research from 2009 to the submission date in 2020,
dealing with the analysis of different components using HILIC.
Results and Conclusion: The literature survey showed that HILIC applications are increasing every
year in pharmaceutical research. It was found that HILIC allows simultaneous analysis of many compounds
using different detectors.