Validated capillary electrophoretic method for the enantiomeric quality control of <i>R</i>‐praziquantel

Szabó, Zoltán‐István; Gál, Réka; Szöcs, Levente; Ludmerczki, Róbert; Muntean, Daniela Lucia; Noszál, Béla; Tóth, Gergő

doi:10.1002/elps.201600492

Cited by 15 publications

(12 citation statements)

References 45 publications

(48 reference statements)

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“…To achieve electrophoretic chiral separation of the uncharged LEN enantiomers, various increasing concentrations (0.2–30 mM) of eight negatively charged, multicomponent CD derivatives were applied, differing in cavity size, type, and number of substituents. Preliminary chiral selector screening was performed with 25 mM Tris‐acetate BGE at pH 5, which also yielded excellent results in our previous studies . The summarized results, presented in Table , reveal that only two CDs displayed chiral interactions with the analyte.…”

Section: Resultsmentioning

confidence: 66%

Chiral separation of lenalidomide by liquid chromatography on polysaccharide‐type stationary phases and by capillary electrophoresis using cyclodextrin selectors

Szabó

Foroughbakhshfasaei

Gál

et al. 2018

J of Separation Science

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Complementary techniques were applied for the investigation of the chiral recognition and enantiomeric resolution of lenalidomide using various cyclodextrins and polysaccharides as chiral selectors. The high-performance liquid chromatography enantioseparation of the anticancer drug was achieved using polysaccharide-type chiral stationary phases in polar organic mode. Elution order and absolute configuration were elucidated by combined circular dichroism spectroscopy and time-dependent density functional theory calculations after the isolation of pure enantiomers. Chiral selector dependent and mobile-phase dependent reversal of the enantiomer elution order was observed, and the nonracemic nature of the lenalidomide sample was also demonstrated. Eight anionic cyclodextrins were screened for their ability to discriminate between the uncharged enantiomers by using capillary electrophoresis. Only two derivatives presented chiral interactions, these cases being interpreted in terms of apparent stability constants and complex mobilities. The best results were delivered by sulfobutylether-β-cyclodextrin, where quasi-equal stability constants were recorded and the enantiodiscrimination process was mainly driven by different mobilities of the transient diastereomeric complexes. The optimized high-performance liquid chromatography (Chiralcel OJ column, pure ethanol with 0.6 mL/min flow rate, 40°C) and capillary electrophoresis methods (30 mM sulfobutylether-β-cyclodextrin, 30 mM phosphate pH 6.5, 12 kV applied voltage, 10°C) were validated for the determination of 0.1% (R)-lenalidomide as a chiral impurity, which could be important if a racemic switch is achieved.

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Section: Resultsmentioning

confidence: 66%

Chiral separation of lenalidomide by liquid chromatography on polysaccharide‐type stationary phases and by capillary electrophoresis using cyclodextrin selectors

Szabó

Foroughbakhshfasaei

Gál

et al. 2018

J of Separation Science

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“…One of the main advantages of CE enantioseparation is the ease of reversing EMO, when compared to chromatographic methods. In our recent study, we have successfully reversed the enantiomer migration order for praziquantel, by polarity switching and EOF reduction at strongly acidic BGE . The same simple approach was employed in this study also, together with reduction of the effective length of the separation capillary to 8.5 cm, by employing short‐end injection technique.…”

Section: Resultsmentioning

confidence: 94%

Chiral separation of rasagiline using sulfobutylether‐β‐cyclodextrin: capillary electrophoresis, NMR and molecular modeling study

et al. 2019

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Pressure‐assisted stereospecific capillary electrophoresis method was developed for the determination of enantiomeric purity of the antiparkinsonian agent (R)‐rasagiline. The optimized method, 50 mM glycine‐HCl buffer pH 2, supplied with 30 mM sulfobutylether‐β‐cyclodextrin, at 35°C, applying 12 kV in reversed polarity, and –8 mbar pressure (vacuum), short‐end injection with ‐25 mbar × 2 s, was successful for baseline separation of rasagiline enantiomers (Rs = 3.5 ± 0.1) in a short analysis time. The method was validated according to current guidelines and proved to be reliable, linear, precise and accurate for determination of 0.15% S‐enantiomer as chiral impurity in R‐rasagiline sample, as well as quantification of the eutomer. Method application was tested on a commercial tablet formulation. Determination of spatial structure of diastereomeric associates was based on 1H and 2D ROESY NMR, indicating that the aromatic moiety of the molecule can enter the cyclodextrin cavity. NMR titration and molecular modeling revealed that S‐rasagiline formed a more stable inclusion complex with sulfobutylether‐β‐cyclodextrin, than its antipode, which is in agreement with electrophoretic results.

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“…By using SBE-β-CD as CS at pH 2.0 to strongly suppress the electroosmotic flow (EOF), the desired EMO (the distomer migrating faster) was obtained and the application of a weak external pressure (8 mbar) allowed the analysis time to be shortened with a concomitant improvement in peak shape, obtaining a QL of the distomer of 0.15% [ 82 ]. In a study for the enantiomeric quality control of R -praziquantel, EMO was reverted by a simple polarity switch (detection end at anode), and suppression of EOF, resulting in increased resolution and migration times (reduced by employing short-end injection) [ 83 ].…”

Section: Recent Advances In the Development Of Ce Analytical Procedur...mentioning

confidence: 99%

New Trends in the Quality Control of Enantiomeric Drugs: Quality by Design-Compliant Development of Chiral Capillary Electrophoresis Methods

et al. 2022

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Capillary electrophoresis (CE) is a potent method for analyzing chiral substances and is commonly used in the enantioseparation and chiral purity control of pharmaceuticals from different matrices. The adoption of Quality by Design (QbD) concepts in analytical method development, optimization and validation is a widespread trend observed in various analytical approaches including chiral CE. The application of Analytical QbD (AQbD) leads to the development of analytical methods based on sound science combined with risk management, and to a well understood process clarifying the influence of method parameters on the analytical output. The Design of Experiments (DoE) method employing chemometric tools is an essential part of QbD-based method development, allowing for the simultaneous evaluation of experimental parameters as well as their interaction. In 2022 the International Council for Harmonization (ICH) released two draft guidelines (ICH Q14 and ICH Q2(R2)) that are intended to encourage more robust analytical procedures. The ICH Q14 guideline intends to harmonize the scientific approaches for analytical procedures’ development, while the Q2(R2) document covers the validation principles for the use of analytical procedures including the recent applications that require multivariate statistical analyses. The aim of this review is to provide an overview of the new prospects for chiral CE method development applied for the enantiomeric purity control of pharmaceuticals using AQbD principles. The review also provides an overview of recent research (2012–2022) on the applicability of CE methods in chiral drug impurity profiling.

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Validated capillary electrophoretic method for the enantiomeric quality control of R‐praziquantel

Cited by 15 publications

References 45 publications

Chiral separation of lenalidomide by liquid chromatography on polysaccharide‐type stationary phases and by capillary electrophoresis using cyclodextrin selectors

Chiral separation of lenalidomide by liquid chromatography on polysaccharide‐type stationary phases and by capillary electrophoresis using cyclodextrin selectors

Chiral separation of rasagiline using sulfobutylether‐β‐cyclodextrin: capillary electrophoresis, NMR and molecular modeling study

New Trends in the Quality Control of Enantiomeric Drugs: Quality by Design-Compliant Development of Chiral Capillary Electrophoresis Methods

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