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

Abstract

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 beta-CD and 4.6 mg/mL sulfated-beta-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.

Two‐chiral component microemulsion EKC – chiral surfactant and chiral oil. Part 2: Diethyl tartrate

“…Chiral products in pharmaceuticals [2][3][4][5][6], agrochemicals [7], and food additives [8,9] are providing the driving force behind this research with recent examples being the CE analyses of the chiral drug etomidate [10], chiral organophosphorus pesticides [11], and amino acids in vinegar [12], respectively. Specifically, the design, production, and analysis of enantiopure formulations, instead of racemates, are becoming more important due to differences in activity between the enantiomers and potential negative side effects from one of the enantiomers [13].…”

Validation of capillary zone electrophoresis and capillary isoelectric focusing separations optimized for the characterization of two recombinant products of the birch pollen allergen Bet v 1a

“…The progressive implementation of CE in industrial quality control of pharmaceuticals [42][43][44] is related to its advanced selectivity [38,39], especially in the separation of closely related proteins [45][46][47]. Further advances of CE compared to alternative separation strategies comprise minute sample consumption in the nL domain and the resolution of different conformations, even if the pI and the hydrodynamic radius are only slightly altered by structural changes [47,48].…”

Comparative study of robustness between micellar electrokinetic capillary chromatography and high-performance liquid chromatography using one-variable-at-a-time and a new multi-variable-at-a-time approach

“…The presented robustness studies in literature [13] are limited to investigation of an influence of basic and internal parameters. These two groups of parameters were described above in the text.…”

“…In the last decade, some studies have been published on the robustness testing for different CE methods [11][12][13][14][15], as well as for different HPLC methods [8,16,17]. A fractional factorial design was used in order to investigate robustness of MEKC method in previously published papers of our research group [18][19][20][21][22].…”