Application of Experimental Design Methodologies in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: A Review

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Aug 7

PMID 34361834

Citations 5

Authors

Gabriel Hancu

Serena Orlandini

Lajos Attila Papp

Adriana Modroiu

Roberto Gotti

Sandra Furlanetto

Affiliations

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Abstract

Chirality is one of the major issues in pharmaceutical research and industry. Capillary electrophoresis (CE) is an interesting alternative to the more frequently used chromatographic techniques in the enantioseparation of pharmaceuticals, and is used for the determination of enantiomeric ratio, enantiomeric purity, and in pharmacokinetic studies. Traditionally, optimization of CE methods is performed using a univariate one factor at a time (OFAT) approach; however, this strategy does not allow for the evaluation of interactions between experimental factors, which may result in ineffective method development and optimization. In the last two decades, Design of Experiments (DoE) has been frequently employed to better understand the multidimensional effects and interactions of the input factors on the output responses of analytical CE methods. DoE can be divided into two types: screening and optimization designs. Furthermore, using Quality by Design (QbD) methodology to develop CE-based enantioselective techniques is becoming increasingly popular. The review presents the current use of DoE methodologies in CE-based enantioresolution method development and provides an overview of DoE applications in the optimization and validation of CE enantioselective procedures in the last 25 years. Moreover, a critical perspective on how different DoE strategies can aid in the optimization of enantioseparation procedures is presented.

Citing Articles

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

Orlandini S, Hancu G, Szabo Z, Modroiu A, Papp L, Gotti R Molecules. 2022; 27(20).

PMID: 36296650 PMC: 9607418. DOI: 10.3390/molecules27207058.

Analysis of drug interactions with serum proteins and related binding agents by affinity capillary electrophoresis: A review.

Sharmeen S, Kyei I, Hatch A, Hage D Electrophoresis. 2022; 43(23-24):2302-2323.

PMID: 36250426 PMC: 10098505. DOI: 10.1002/elps.202200191.

Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization.

Carcu-Dobrin M, Hancu G, Papp L, Fulop I Molecules. 2022; 27(17).

PMID: 36080370 PMC: 9458186. DOI: 10.3390/molecules27175603.

Quality by Design Assisted Optimization of a Chiral Capillary Electrokinetic Chromatographic Method for the Separation of Amlodipine Enantiomers Using Maltodextrin as Chiral Selector.

Ratih R, Watzig H, Stein M, El Deeb S Pharmaceuticals (Basel). 2022; 15(3).

PMID: 35337117 PMC: 8955793. DOI: 10.3390/ph15030319.

Single Isomer -Heterocyclic Cyclodextrin Derivatives as Chiral Selectors in Capillary Electrophoresis.

Fejos I, Kalydi E, Kukk E, Seggio M, Malanga M, Beni S Molecules. 2021; 26(17).

PMID: 34500704 PMC: 8434369. DOI: 10.3390/molecules26175271.

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