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

Abstract

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.

Keywords:

• Ezetimibe
• high-performance liquid chromatography
• analytical methods
• degradation products
• process-related impurities

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Funding

The authors acknowledge Coordination for the Improvement of Higher Education Personnel (CAPES), Carlos Chagas Filho Research Support Foundation of Rio de Janeiro State (FAPERJ) and National Council for Scientific and Technological Development (CNPq). Funding information in Portuguese: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). There is no specific grant number from these agencies for this manuscript. These agencies contribute to the payment of undergraduate and graduate scholarships, as well as continuously contributing materials for use in the laboratory.