Enantiomeric assay of escitalopramS(+)‐enantiomer and its “in‐process impurities” using two different techniques

Abstract

The enantiomeric purity of escitalopram oxalate ESC and its "in-process impurities," namely, ESC-N-oxide, ESC-citadiol, and R(−)-enantiomer were studied in drug substance and products using high-performance liquid chromatography (HPLC)-UV (Method I), synchronous fluorescence spectroscopy (SFS) (Method IIA), and first derivative SFS (Method IIB). Method I describes as an isocratic HPLC-UV for the direct resolution and determination of enantiomeric purity of ESC and its "in-process impurities." The proposed method involved the use of α l -acid glycoprotein (AGP) chiral stationary phase. The regression plots revealed good linear relationships of concentration range of 0.25 to 100 and 0.25 to 10 μg mL −1 for ESC and its impurities. The limits of detection and quantifications for ESC were 0.075 and 0.235 μg mL −1 , respectively. Method II involves the significant enhancement of the fluorescence intensities of ESC and its impurities through inclusion complexes formation with hydroxyl propyl-β-cyclodextrin as a chiral selector in Micliavain buffer. Method IIA describes SFS technique for assay of ESC at 225 nm in presence of its impurities: R(−)-enantiomer, citadiol, and N-oxide at Δλ of 100 nm. This method was extended to (Method IIB) to apply first derivative SFS for the simultaneous determination of ESC at 236 nm and its impurities: the R(−)-enantiomer, citadiol, and N-oxide at 308, 275, and 280 nm, respectively. Linearity ranges were found to be 0.01 to 1.0 μg mL −1 for ESC and its impurities with lower detection and quantification limits of 0.033/0.011 and 0.038/0.013 μg mL −1 for SFS and first derivative synchronous fluorescence spectra (FDSFS), respectively. The methods were used to investigate the enantiomeric purity of escitalopram.KEYWORDS enantioselective analysis, escitalopram, in-process impurities, R(−)-enantiomer, synchronous fluorescence spectroscopy, α l -acid glycoprotein

An overview of chiral separations of pharmaceutically active substances by HPLC (2018–2020)

“…Enantioselective separation of eight antihistamines and chiral separation of pheniramine and its enantioselective pharmacokinetics in rat plasma were performed on an alpha-1-acid glycoprotein-based Chiralpak AGP column [ 88 , 89 ]. The use of a Chiralpak AGP column for the analysis of S -(+)-escitalopram, a selective serotonin reuptake inhibitor, was also described [ 90 ]. A Daicel Chiralpak MA (+) stationary phase composed of N , N -dioctyl- l -alanine was used for determination of the absolute configuration of ikoamide, an antimalarial lipopeptide from Okeania sp.…”

EnantioselectiveLCanalysis and determination of selective serotonin reuptake inhibitors

“…In a recent study, (Soliman, ), the enantiomeric purity of oxalate derivative of ( S )‐(+)‐enantiomer of citalopram (ECtp, escitalopram), and its “in‐process impurities,” namely, ECtp‐ N‐ oxide, ECtp‐citadiol and ( R ) ‐ (−)‐enantiomer, were analyzed in drug substances and products using three different methods. In Method 1, an isocratic HPLC–UV for direct separation and determination of enantiomeric purity of ECtp and its “in‐process impurities” were determined; the method involved the use of a Chiral‐AGP column.…”

Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose‐based chiral stationary phase under normal‐ and green reversed‐phase conditions

“…To overcome these problems, alternative analytical approaches utilizing different CSPs have been published [3]. The methods available in the literature for the enantioseparation of CIT are based on different types of selectors such as cellulose tris(3-chloro-4-methylphenylcarbamate) [4], amylose tris(3,5-dimethylphenylcarbamate) [5], α l -acid glycoprotein [6], phenylcarbamated β-cyclodextrin [7], cellulose F I G U R E 1 Structures of escitalopram oxalate (ESC) and its chiral impurities A, B, C, H, and K tris(3,5-dimethylphenylcarbamate) [8][9][10], and cellulose tris(phenylcarbamate) [11].…”