A validated enantiospecific method for determination and purity assay of clopridogrel

Autor: Katarina Nikolic, Danica Agbaba, Željka Bešović, Slavko Marković, Branka Ivković
Rok vydání: 2009
Předmět:
Models
Molecular
chiral separation
Ticlopidine
Resolution (mass spectrometry)
Analytical chemistry
Guidelines as Topic
cyclodextrin-based chiral stationary phase
01 natural sciences
Catalysis
Analytical Chemistry
Structure-Activity Relationship
chemistry.chemical_compound
Impurity
Phase (matter)
Drug Discovery
Technology
Pharmaceutical
Acetonitrile
Chromatography
High Pressure Liquid
Spectroscopy
Pharmacology
Detection limit
clopidogrel
Chromatography
Molecular Structure
010405 organic chemistry
Chemistry
beta-Cyclodextrins
010401 analytical chemistry
Organic Chemistry
Computational Biology
Reproducibility of Results
Stereoisomerism
Hydrogen-Ion Concentration
Reference Standards
Clopidogrel
0104 chemical sciences
enantiomeric impurity
Calibration
Thermodynamics
Biological Assay
Spectrophotometry
Ultraviolet
Methanol
Enantiomer
Drug Contamination
Chirality (chemistry)
Platelet Aggregation Inhibitors
Tablets
Zdroj: Chirality
ISSN: 1520-636X
0899-0042
DOI: 10.1002/chir.20681
Popis: A new and accurate HPLC method using b-cyclodextrin chemically bonded to spherical silica particles as chiral stationary phase (CSP) was developed and validated for determination of S-clopidogrel and its impurities R-enantiomer and S-acid as a hydrolytic product. The effects of acetonitrile and methanol content in the mobile phase and temperature on the resolution and retention of enantiomers were investi- gated. A satisfactory resolution of S-clopidogrel active form and its impurities was achieved on ChiraDex 1 column (5 lm, 4 3 250 mm) at a flow rate of 1.0 ml/min and 178C using acetonitrile, methanol and 0.01 M potassium dihydrogen phosphate solution (15:5:80 v/v/v) as mobile phase. The detection wavelength was set at 220 nm. The method was validated in terms of accuracy, precision, linearity, and robustness. The limit of detection for R-enantiomer and S-acid were 0.75 and 0.09 lg/ml, respectively, injection volume being 20 ll. Finally, the molecular modeling of the inclusion com- plexes between the analytes and b-cyclodextrin was performed to investigate the mechanism of the enantiorecognition and to study the quantitative structure-retention relationships. Chirality 21:878-885, 2009. V C 2008 Wiley-Liss, Inc.
Databáze: OpenAIRE
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