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

Ratih Ratih,Hermann Wätzig,Sami El Deeb,Matthias Oliver Stein

doi:10.3390/ph15030319

Abstract

Analytical-method development based on design of experiment has been applied for optimizing the enantioseparation of amlodipine by chiral capillary electrokinetic chromatography using maltodextrin as the chiral selector. The effect of different factors on the enantioresolution quality was screened. Three separation factors, namely maltodextrin concentration, pH of the background electrolyte and applied voltage were selected as independent variables. The number of experiments was reduced while maximizing the information content using design of experiment. Based on a full-quadratic design that included three variables on three levels, the total design space could be reduced to fifteen factor combinations using a D-optimal algorithm. The aim of the experiment was to find the optimal factor combinations with respect to resolution. The maltodextrin concentration (7.5–10% w/v) demonstrated the strongest effect on the resolution followed by pH (2–4) of the background electrolyte and the applied voltage (15–20 kV). An increase in the maltodextrin concentration was found to result in a greater stereoselectivity, represented by the higher resolution values (Rs ≥ 1.5). The separation conditions in the proposed method were feasible to be adjusted within the applied range with an acceptable resolution.

Highlights

Chiral separations using chiral stationary phases in liquid chromatography and buffer additives in capillary electrophoresis (CE) are the techniques of choice for analytical purposes
MD dextrose equivalent (DE) (4–7) at concentrations of 7.5–10% w/v was employed as the chiral selector, the background electrolyte (BGE) was adjusted to pH values between 2.0 and 4.0 and the applied voltage ranged from 15 to 20 kV
Systematic method optimization with a design of experiment was applied using Doptimal design to investigate the combinations of separation factors in maltodextrin-based chiral electrokinetic chromatography (cEKC)

Summary

Introduction

Chiral separations using chiral stationary phases in liquid chromatography and buffer additives in capillary electrophoresis (CE) are the techniques of choice for analytical purposes. Chiral CE offers more simplicity in changing the employed chiral selector and adjusting its concentration in the background electrolyte (BGE) [1,2]. Since the chiral selector in the BGE acts as pseudostationary phase and the separation follows chromatograpic principles, the term chiral electrokinetic chromatography (cEKC) is used to describe chiral CE [3,4]. Cyclodextrines have become the most common chiral selectors. Due to its hydrophobic cavity, it shows chiral recognition toward various drug enantiomers [5–7]. The hydrophobic properties of the inner helical structure lead to similar characteristics as the cyclodextrins’ cavity [8]. Maltodextrins are oligosaccharides which can be characterized by a dextrose equivalent (DE)

Methods

Discussion

Conclusion