title: Validated capillary electrophoretic method for the enantiomeric quality control of R-praziquantel.
abstract: The enantiomers of praziquantel, the drug of choice in schistosomiasis, were separated by electrokinetic chromatography with cyclodextrins. Nine anionic cyclodextrins were screened for their ability to discriminate between the uncharged enantiomers. Seven investigated selectors presented chiral interactions with the enantiomers, these cases being interpreted in terms of stability constants and complex mobilities. The best results were delivered by sulfated-β-cyclodextrin, where quasi-equal stability constants were accompanied by extreme selectivity values and was explained on the basis of highly different mobilities of the transient diastereomeric complexes. Since the enantiomer migration order was unfavorable, a simple polarity switch was employed (detection end at anode), which apart from migration order reversal, also resulted in extreme resolution values (Rs> 35) and increased migration times. After optimization (50 mM phosphate buffer pH 2.0, supplied with 15 mM sulfated-β-cyclodextrin, 15 kV, capillary temperature 25°C, short-end injection with 50 mbar × 2 s), analysis time under 10 min were obtained, while still maintaining high resolution (Rs> 10). The method was validated according to the ICH guidelines and application of the method was tested on in-house synthetized R-praziquantel batches and on commercial, combination tablets containing racemic mixture of the drug.
authors.affiliation: Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureș, Tîrgu Mureș, Romania.
authors.forename: Zoltán-István
authors.initials: ZI
authors.lastname: Szabó
authors.affiliation: Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureș, Tîrgu Mureș, Romania.
authors.forename: Réka
authors.initials: R
authors.lastname: Gál
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Szőcs
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Ludmerczki
authors.affiliation: Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureș, Tîrgu Mureș, Romania.
authors.forename: Daniela-Lucia
authors.initials: DL
authors.lastname: Muntean
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
authors.forename: Gergő
authors.initials: G
authors.lastname: Tóth
mesh_terms: D019075:Electrophoresis, Capillary / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D011223:Praziquantel / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification* / Q000592:standards; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D011223:Praziquantel
keywords: Chiral separation; Chiral switch; Cyclodextrin; Enantioseparation; Schistosomiasis