Background: During the development, dosage optimization and safety evaluation of a drug, rapid and
precise monitoring of an administered drug and/or its metabolites in biological samples. As drug biotransformation
produces more hydrophilic metabolites for the enhancement of drug elimination, it often presents a challenge for
traditional reversed-phase liquid chromatography (RPLC) separation. Because hydrophilic interaction liquid chromatography
(HILIC) is capable of retaining polar compounds and is readily compatible with mass spectrometry
(MS), HILIC has been used as a complementary separation technique to RPLC for the analysis of polar metabolites,
especially polar drugs and their metabolites.
Methods: We undertook a comprehensive search of databases for HILIC-related research literature. The characteristics
including method, result and innovation of screened papers were described, and an inductive and analytical method was applied to
analyze those studies using a reasonable framework.
Results: This paper covers core aspects of the HILIC-MS/MS method and the overall profile of its application in drug and/or its metabolites
analysis by reviewing 102 papers. The emphasis of this paper has been placed on the applications of the HILIC-MS/MS method in
quantitative bioanalysis of drugs alone or along with their metabolites in drug metabolism studies in recent years. As a fundamental and
critical step of the bioanalytical method, conventional sample preparation techniques of biological matrices for the HILIC-MS/MS analysis
of drugs and/or their metabolites are also briefly featured.
Conclusion: The findings of this review confirm the powder of HILIC-MS/MS methods in the separation and quantification of drugs
and/or their metabolites.