First synthesis and characterization of SRR/RSS-Ezetimibe

Ren, Yun; Li, RenJun; Deng, Yong; Guan, Mei; Wu, Yong; Li, Hai

doi:10.1016/j.tetlet.2013.09.049

Cited by 11 publications

(4 citation statements)

References 5 publications

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“…The overall acceptable daily dose level to be considered is 0.1%. A number of reports on the identification, development and characterization of ezetimiberelated impurities and their degradants were published [9][10][11][12][13][14][15] . Four process-related impurities 4- (impurity -STG -01) were identified during the manufacturing of ezetimibe drug substance.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2021

IJPSR

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The gradient HPLC method was developed to detect and quantify four related substances (FIP, FHO-2, STG-01, and desfluoro) in ezetimibe drug material. The efficient separation was carried out on Water X-Select CSH C18 column (4.6 mm × 100 mm, 2.5 μm). The impurities were separated in gradient mode of elution with 0.1% trifluoroacetic acid in water (mobile phase A) and 0.1% trifluoroacetic acid in acetonitrile (mobile phase B) at a flow rate of 1.0 ml /min. The effluents were detected at 254 nm. The method has been validated in compliance with the regulatory standards suggested by the International Conference on Harmonization. The parameters validated included precision, linearity, detection limit, quantification limit, specificity, accuracy, and robustness. The method showed good linearity from 0.03 μg/ml to 1.5 μg/ml for FIP, FHO-2, STG-01, and desfluoro. The developed method was applied to determine the studied impurities in three different batches of ezetimibe drug material. The method proposed in this work could be employed in quality control of ezetimibe bulk drug.

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Section: Introductionmentioning

confidence: 99%

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2021

IJPSR

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“…Quantification of chiral drugs in the presence of binary mixture, especially the analysis of the two components at the same time is challenging. A few methods for the determination of isomeric EZM were reported in literature, such as HPLC, SFC, and nuclear magnetic resonance (NMR), which in general disconfirm the efficient analysis of multiple components and have limitations of complex pretreatment, large sample amount, etc. Therefore, it is essential to find an effective way to analyze the chiral purity of EZM and ATO simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Direct differentiation of stereoisomers of ezetimibe/ambrisentan/atorvastatin and their mechanism study by electrospray ionization quadrupole time‐of‐flight mass spectrometry

Wang

et al. 2018

J Mass Spectrom

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A mass spectrometric method is introduced for rapid and accurate chiral quantification by examining a trimeric metal complex into which a chiral reference is incorporated with the analyte. Several metal ions (CuII, NiII, MgII, MnII, CoII, and ZnII) were selected as the central metal ion, and chiral drugs ezetimibe (EZM) and ambrisentan (AMB) were used as the reference to each other for isomeric differentiation by using electrospray ionization quadrupole time‐of‐flight mass spectrometry. Doubly charged trimeric cluster ions instead of the singly charged clusters were applied in this study. Kinetic method (KM) and chiral recognition (CR) method were used for construction of a calibration curve for chiral quantitation. The results from the two methods were found to be complementary to each other, which improved quantitative analysis of stereoisomers for EZM. Furthermore, we have successfully used S‐AMB as reference for the chiral differentiation of enantiomeric atorvastatin (ATO), which is frequently combined with EZM as a codrug. Experimental results showed that the binary mixture of EZM and ATO enantiomers can be determined simultaneously without prior separation steps. The direct measurement of chiral purity within 5% was demonstrated. This mass spectrometric method represents an effective alternative to commonly used chromatographic techniques as means of chiral purity determination and is of potential use in rapid screening experiments.

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“…Few analytical methods have been reported in the literature for the determination of ezetimibe including studies on its pharmaceutical dosage forms and degradation studies [18] , [19] , [20] , [21] . In recent years, studies related to identification, synthesis and characterization of process and degradation related impurities, including stereoisomers of ezetimibe, have been reported [22] , [23] , [24] , [25] , [26] , [27] , [28] .…”

Section: Introductionmentioning

confidence: 99%

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

Atici

Karliga

2015

Journal of Pharmaceutical Analysis

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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.

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First synthesis and characterization of SRR/RSS-Ezetimibe

Cited by 11 publications

References 5 publications

Untitled

Untitled

Direct differentiation of stereoisomers of ezetimibe/ambrisentan/atorvastatin and their mechanism study by electrospray ionization quadrupole time‐of‐flight mass spectrometry

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

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