Separation of etodolac enantiomers by capillary electrophoresis. Validation and application of the chiral method to the analysis of commercial formulations

Abstract

Separation of etodolac enantiomers by capillary electrophoresis. Validation and application of the chiral method to the analysis of commercial formulationsSeparation of etodolac enantiomers, which exhibit different biological activity and pharmacokinetic profiles, has been achieved using the randomly substituted (2-hydroxy)propyl-b-cyclodextrin (HP-b-CD) as chiral selector in capillary electrophoresis. The selection of this CD was made after screening of different CD derivatives of neutral and anionic nature. The effect on the enantioresolution of the buffer concentration and of the degree of substitution (DS) and concentration of the CD as well as of instrumental parameters, such as the capillary temperature and the separation voltage, were studied. The highest resolution of etodolac enantiomers was around 2.5 using 100 mM phosphate buffer (pH 7.0) with 20 mM HP-b-CD (DS , 4.2) and UV detection at 225 (10) nm with a reference wavelength at 360 (50) nm. Validation of the chiral method in terms of selectivity, linearity, precision (instrumental repeatability, method repeatability, intermediate precision), and the limits of detection and quantitation allowed to evaluate its quality to the analysis of etodolac enantiomers in different pharmaceutical preparations containing racemic etodolac.

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…In many cases, a wide spectrum of selectors was screened with anionic CDs outperforming neutral CDs because of the former's countermigration property and ability to electrostatically interact with positive enantiomers. One exception was the negatively charged enantiomers of etodolac, in which a series of eight neutral CDs and five anionic CDs were studied with only HP-b-CD and g-CD showing promise [76]; a method using HP-b-CD was subsequently optimized and validated.…”

Determination of enantiomeric impurity of etodolac by capillary electrophoresis using (2-hydroxypropyl)-β-cyclodextrin

“…The assay is specific allowing the detection of the impurities at the R-(-)-etodolac concentration 0.2% with hight resolution of 4.0. This resolution (4.0) was higher than that (2.5) of a previous method (Pablos et al, 2005). Moreover, ketoprofen was used as an internal standard for improving peak area precision (ketoprofen doesn't show any chiral separation in our condition although ketoprofen is a chiral compound).…”

“…However, only with the permethylated γ-CD (Chirasil-Dex) it was possible to achieve a resolution of 1.6 for etodolac enantiomers in 30 min. According to Pablos's report on the separation of etodolac enantiomers by capillary electrophoresis, validation and application of the chiral method to the analysis of racemic etodolac commmercial formulations, it was possible to achieve a resolution of 2.5 for racemic etodolac (Pablos et al, 2005). However, with the resolution of 2.5 it was difficult for the chiral purity test of etodolac enantiomers.…”

Recent advances in pharmaceutical applications of chiral capillary electrophoresis

“…Quantitation of the six piperazine compounds was also performed with this method, on urine samples with liquid-liquid and solid phase extraction (SPE) and synthesized samples of piperazine. In another publication by de Pablos et al, HP-␤-CD even showed the best selectivity among 13 different neutral and anionic CD derivatives towards etodolac enantiomers [12]. Being aware of the reproducibility problem of randomly substituted CDs (RS-CDs), HP-␤-CD from three different suppliers were tested at different concentrations.…”