Development and Validation of a Chiral HPLC Method for Quantitative Analysis of Enantiomeric Escitalopram

Abstract

ABSTRACT:In the present study a rapid, accurate and precise chiral HPLC method was developed and validated for enantiomeric separation of racemate citalopram and escitalopram according to the guidelines of United States of Pharmacopeia (USP) and International Conference on Harmonization (ICH). The chiral chromatographic separation was achieved with ammonium acetate/ ethanol/ 2-propanol/ methylene dichloride (100 : 150 : 70 : 30, v/v) at a flow rate of 0.5 ml/min using a chiral CD-PH column. The HPLC analyses were monitored at 254 nm. The method showed a good linearity with regression coefficient (r 2 ) of 0.998 in the range of 20.0-70.0 µg/ml for escitalopram. The detection limit (LOD), quantitation limit (LOQ) and average percentage of recovery for escitalopram were found to be 2.54, 7.68 µg/ml and 100.28% to 102.86%, respectively. The percentage of relative standard deviation (%RSD) for intra-and inter-day precision were found as 0.16% and 0.09%, respectively. The established method proved as reproducible with a %RSD value of less than 2 and having the robustness within specified limit. The present study also showed the enantiomeric purity or excess (%ee) of seven pharmaceutical preparations of escitalopram. Thus the proposed chiral method can be applied for the enantiomeric purity determination of escitalopram formulations.

Selective LC–MS/MS determination of citalopram enantiomers and application to a pharmacokinetic evaluation of generic and reference formulations

“…As observed, stationary phases consisted of silica chemically bound to n-alkyl groups (C18, CN, Select B) (Bhimanadhuni et al, 2012;De Sousa et al, 2012;El-Gindy et al, 2006;Malfará et al, 2007;Peng et al, 2016;Ragab & Bahgat, 2019;Skibi nski & Misztal, 2007), chiral selectors (β-cyclodextrin or cellulose derivatives) (Geryk et al, 2013;Haupt, 1996;Hegstad et al, 2017;Kosel et al, 1998;Rahman et al, 2017;Rocha et al, 2007;et al, 1995a, 1995bWeisskopf et al, 2016), and sol-gel capillary monolith (Johannesson & Bergquist, 2007). The HPLC coupled to FL (Kosel et al, 1998;Rochat et al, 1995aRochat et al, , 1995b, UV (Bhimanadhuni et al, 2012;El-Gindy et al, 2006;Geryk et al, 2013;Haupt, 1996;Malfará et al, 2007;Peng et al, 2016;Ragab & Bahgat, 2019;Rahman et al, 2017;Skibi nski & Misztal, 2007;Zheng et al, 2000), or MS/MS detectors (De Sousa et al, 2012;Golovko et al, 2016;Hegstad et al, 2017;Rocha et al, 2007;Weisskopf et al, 2016) was applied to quantify the (R/S)-CTP and/or the enantiomers in plasma, milk, soil, tissues, raw material, and formulations. Additional analytical techniques such as ultra-high performance supercritical fluid chromatography-MS/MS (Hegstad et al, 2017) and capillary electrophoresis instrument coupled to time-of-fligh...…”

“…The HPLC methods with UV or FL detection described until now (Table 5) were applied to assess the quality of the raw materials and drug formulations (Bhimanadhuni et al, 2012;El-Gindy et al, 2006;Geryk et al, 2013;Peng et al, 2016;Ragab & Bahgat, 2019;Rahman et al, 2017), as well as the drug plasma concentrations (Haupt, 1996;Kosel et al, 1998;Malfará et al, 2007;Ragab & Bahgat, 2019;Rochat et al, 1995aRochat et al, , 1995bZheng et al, 2000). However, their longer running time, lower sensitivity, and selectivity compared to the LC-MS/MS methods may limit their applications in pharmacokinetic studies, specially due the long halflife of (R/S)-CTP (Pollock, 2001) and (S)-CTP (Pastoor & Gobburu, 2014).…”

Chiral analysis of E‐ε‐viniferin enantiomers, towards a new chemotaxonomic marker of the vine

“…The enantiomeric excess is a historical and current chemical parameter used as a reference for deciphering an enantiomeric composition. It is largely applied in pharmacopeia methods, 16,17 and several authors working on polyphenol/stilbene enantiomers have used it. [18][19][20][21] Due to the variation in genotype and phenotype of the various cultivars, these values can vary substantially.…”

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].…”