Ezetimibe: A Review of Analytical Methods for the Drug Substance, Pharmaceutical Formulations and Biological Matrices

Ezetimibe (EZM) is a selective inhibitor of the sterol transporter Niemann-Pick C1-Like 1 in the small intestine used as an adjunctive therapy to lower cholesterol levels in cases of hyperlipidemia. The goal of this work was to summarize the main physical-chemical, pharmacological and pharmacokinetic characteristics of EZM, as well as to describe the main analytical methodologies for the quantification of the drug. Methods described in the United States Pharmacopeia for EZM raw material and tablets were also presented. The drug has a large number of process-related impurities and degradation products and needs strict quality control of its impurities. Specific chiral methods for the evaluation of its chiral impurities are also a need for EZM. The main advantages and disadvantages of the compiled analytical methods were presented, as well as the limits of detection and quantitation. The fastest and most efficient methods were highlighted. Most methods for analyzing EZM used C₈ or C₁₈ stationary phases in gradient mode with binary mobile phases containing acetonitrile and an acidic buffer solution with ultraviolet detection. For analysis of EZM in biological matrices, liquid chromatography-tandem mass spectrometry is generally employed using electron spray ionization in negative ionization mode using multiple reaction monitoring. Different methods in the literature evaluate a large number of impurities for EZM, however new stability-indicating high-performance liquid chromatography methods for the drug are still needed.