title: Validated Densitometric TLC-Method for the Simultaneous Analysis of (R)- and (S)-Citalopram and its Related Substances Using Macrocyclic Antibiotic as a Chiral Selector: Application to the Determination of Enantiomeric Purity of Escitalopram.
abstract: A novel economic procedure for the simultaneous stereospecific separation and analysis of (R)- and (S)-citalopram and its related substances or impurities has been developed and validated. Chromatography was performed on silica gel 60 F254 plates with acetonitrile: methanol: water (15:2.5:2.5: v/v/v) as a mobile phase containing 1.5 mM norvancomycin or 2.5 mM vancomycin as a selector at ambient temperature. (R)- and (S)-citalopram enantiomers in presence of its related substances; citalopram citadiol and citalopram N-oxide were well separated with significant Rf values of 0.33 ± 0.02, 0.85 ± 0.02, 0.45 ± 0.02 and 0.22 ± 0.02, respectively. The spots were detected with either iodine vapor, or by use of a UV lamp followed by densitometric measurement at 239 nm. All variables affecting the resolution, such as concentration of chiral selectors, mobile phase system at different temperatures and pH-values were investigated and the conditions were optimized. Calibration plots for analysis of (R)- and (S)-enantiomers were linear in the range of 0.2-16.8 μg/10 μl (R≥0.9994, n=6) with acceptable precision (%RSD<2.0) and accuracy (99.70 ± 0.85% and 99.51 ± 0.61% for (S)-citalopram and escitalopram, respectively). The limit of detection and quantification were 0.08 μg/10 μl and 0.25 μg/10 μl, respectively, for (R)- and (S)-citalopram. The proposed method is simple, selective, and robust and can be applied for quantitative determination of enantiomeric purity of (R)- and (S)-citalopram (escitalopram) as well as the related impurities in drug substances and pharmaceutical preparations. The method can be useful to investigate adulteration of pure isomer with the cheep racemic form.
authors.affiliation: National Organization for Drug Control and Research (NODCAR), Egypt.
authors.forename: Suzan Mahmoud
authors.initials: SM
authors.lastname: Soliman
keywords: (R)- and (S)-citalopram; TLC-determination; enantiomers; norvancomvcin; pharmaceutical preparations; related substance