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Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system
Author(s) -
Hammitzsch Manuela,
Rao Ramisetti N.,
Scriba Gerhard K. E.
Publication year - 2006
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200600257
Subject(s) - chromatography , capillary electrophoresis , chemistry , enantiomer , linearity , cyclodextrin , calibration curve , normalization (sociology) , accuracy and precision , etomidate , analytical chemistry (journal) , detection limit , mathematics , stereochemistry , pharmacology , physics , statistics , quantum mechanics , sociology , anthropology , medicine , propofol
An enantioselective CE assay for the simultaneous determination of the enantiomeric purity and of related substances of etomidate has been developed and validated using a binary chiral selector system employing 30 mg/mL β‐CD and 4.6 mg/mL sulfated‐β‐CD in a 150 mM potassium phosphate buffer, pH 2.1. The method was validated with respect to specificity, range, linearity, LOQ and LOD, precision and accuracy. The assay allowed the detection and determination of related substances including ( S )‐etomidate at the 0.05% w/w level, the reporting threshold as defined by the International Conference on Harmonisation guidelines as well as the European Pharmacopoeia. Robustness testing was carried out by an “Augmented Plackett–Burman” design. Quantitation of the compounds was performed by calibration graphs with respect to lidocaine hydrochloride as internal standard and by peak area normalization, the procedure usually applied by pharmacopoeias. Although data obtained from the calibration graphs constructed with the aid of the internal standard were more accurate based on compound recovery, peak area normalization may also be used without significant loss of accuracy and precision.