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

Abstract

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.

Chiral Analysis of the Key Intermediates of Tenofovir Alafenamide Fumarate

“…[1][2][3] Stereoisomers introduced into the human body could exhibit different pharmacokinetic, pharmacodynamic, and toxicologic profiles. 4 Therefore, chiral purity control of optically active drug substances is essential for the integrity and quality of related drug products. TAF is a chiral drug chemically belonging to acyclic nucleoside phosphonates.…”

Fast and precise chiroptical spectroscopy by photoelectron elliptical dichroism

“…1 Quality control thus requires to determine the enantiomeric excess of these compounds with a 0.05% error bar. 2 Such measurements are routinely performed by chiral chromatography, relying on the different migration times of the two enantiomers through a chiral column. 2 However, the speed of chromatographic measurements is intrinsically limited by the migration time needed for baseline resolving a pair of enantiomers.…”

Quality by design‐guided development of a capillary electrophoresis method for the simultaneous chiral purity determination and impurity profiling of tamsulosin

“…Therefore, the aim of the present study was to develop a CE method for the determination of TAM enantiomeric purity and some chemically related impurities (Figure 1) using CDs as chiral selectors and applying analytical quality by design (AQbD) methodology for rational method development. This approach, which is increasingly used in CE and involves multivariate techniques such as DoE, identifies the critical process parameters (CPPs) as the experimental factors affecting the critical quality attributes (CQAs) of the method and results in an understanding of their effects so that they can be controlled appropriately [25][26][27][28][29]. Furthermore, the draft guideline Q14 "Analytical Procedure Development" of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) highlights the application of scientific and riskbased methods to create and sustain analytical methods for the evaluation of the quality of drug substances and products [29,30].…”

“…This approach, which is increasingly used in CE and involves multivariate techniques such as DoE, identifies the critical process parameters (CPPs) as the experimental factors affecting the critical quality attributes (CQAs) of the method and results in an understanding of their effects so that they can be controlled appropriately [25][26][27][28][29]. Furthermore, the draft guideline Q14 "Analytical Procedure Development" of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) highlights the application of scientific and riskbased methods to create and sustain analytical methods for the evaluation of the quality of drug substances and products [29,30]. Annex A of the guideline specifically refers to CE as a suitable method for the determination of the chiral purity of drugs (sakarutinib maleate in this case) to meet the performance criteria defined in the analytical target profile (ATP).…”