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Quality by Design-Based Development of a Chiral Capillary Electrophoresis Method for the Determination of Dextrodropropizine and 1-Phenylpiperazine as Impurities of Levodropropizine

  • Stephan Niedermeier
  • Gerhard K. E. ScribaEmail author
Short Communication
  • 18 Downloads

Abstract

Based on a quality by design approach, a capillary electrophoresis method for the simultaneous determination of dextrodropropizine and the achiral precursor 1-phenylpiperazine in levodropropizine was developed. The analytical target profile was defined as a method allowing the simultaneous determination below the 0.5% level within a maximum analysis time of 20 min with an acceptable precision and accuracy. Based on scouting experiments, sulfated β-cyclodextrin in a 25 mM potassium phosphate buffer, pH 7.0, was selected. Subsequently, cyclodextrin concentration, propan-2-ol concentration, capillary temperature and applied voltage were identified as critical process parameters using a full factorial design followed by a central composite face-centered design for the final optimization of cyclodextrin concentration and temperature. The design space was obtained by Monte Carlo simulations. The final method comprised a 40/50.2 cm effective/total length, 75 µm inner diameter fused-silica-capillary, 25 mM potassium phosphate buffer, pH 7.0, containing 23.5 mg mL−1 sulfated β-cyclodextrin and 10% (v/v) propan-2-ol as background electrolyte, 16.3 °C capillary temperature and an applied voltage of 16.5 kV. The robustness was assessed using a Plackett–Burman design followed by method validation. Finally, the method was applied to the analysis levodropropizine reference substance of the European Pharmacopoeia and a liquid dosage form.

Keywords

Capillary electrophoresis Chiral separation Levodropropizine Quality by design Enantiomeric purity 

Notes

Acknowledgments

The gift of Quimbo® drops by Noweda (Essen, Germany) is gratefully acknowledged.

Complilance with Ethical Standards

Conflict of Interest

The authors have declared no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10337_2019_3817_MOESM1_ESM.docx (1.1 mb)
Supplementary material 1 (DOCX 1114 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical and Medicinal ChemistryFriedrich Schiller University JenaJenaGermany

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