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Identification, synthesis and characterization of process related desfluoro impurity of ezetimibe and HPLC method validations.

ABSTRACT: Ezetimibe, which selectively inhibits cholesterol absorption across the intestinal wall and is used as an antihyperlipidemic agent, is synthesized for commercial use as a drug substance in highly pure form. During the synthetic process development studies of ezetimibe, an impurity was detected in the final product at levels ranging from 0.05% to 0.15% in reverse phase gradient high performance liquid chromatography (HPLC) method and its molecular weight was determined by LC-MS analysis. The impurity was identified as (3R,4S)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)-1-phenylazetidin-2-one which is called desfluoro ezetimibe (lactam-related) impurity, synthesized and characterized, the mechanism of its formation was discussed in detail. After all standardization procedures, it was used as a reference standard during validation of HPLC method and routine analyses. In addition, content of Eze-1 desfluoro impurity in Eze-1 intermediates was specified as 0.10% to keep the formation of desfluoro ezetimibe impurity under control and the related substances HPLC method was validated accordingly.

SUBMITTER: Bellur Atici E

PROVIDER: S-EPMC5762248 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Identification, synthesis and characterization of process related desfluoro impurity of ezetimibe and HPLC method validations.

Bellur Atici Esen E Karlığa Bekir B

Journal of pharmaceutical analysis 20150424 6

Ezetimibe, which selectively inhibits cholesterol absorption across the intestinal wall and is used as an antihyperlipidemic agent, is synthesized for commercial use as a drug substance in highly pure form. During the synthetic process development studies of ezetimibe, an impurity was detected in the final product at levels ranging from 0.05% to 0.15% in reverse phase gradient high performance liquid chromatography (HPLC) method and its molecular weight was determined by LC-MS analysis. The impu ...[more]

PMID: 29403950

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Dataset Information

Identification, synthesis and characterization of process related desfluoro impurity of ezetimibe and HPLC method validations.

Publications

Identification, synthesis and characterization of process related desfluoro impurity of ezetimibe and HPLC method validations.

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