A new and fast DLLME-CE method for the enantioselective analysis of zopiclone and its active metabolite after fungal biotransformation

Journal of Pharmaceutical and Biomedical Analysis
Nayara Cristina Perez de AlbuquerqueAnderson Rodrigo Moraes de Oliveira

Abstract

Zopiclone (ZO) is a chiral drug that undergoes extensive metabolism to N-desmethylzopiclone (N-Des-ZO) and zopiclone-N-oxide (N-Ox-ZO). Pharmacological studies have shown (S)-N-Des-ZO metabolite presents anxiolytic activity and a patent for this metabolite was requested for anxiety treatment and related disorders. In this context, biotransformation employing fungi may be a promising strategy to obtain N-Des-ZO. To perform the biotransformation study in this work, an enantioselective method based on capillary electrophoresis (CE) and dispersive liquid-liquid microextraction (DLLME) was developed. CE analyses were carried out in sodium phosphate buffer (pH 2.5; 50mmolL(-1)) containing 0.5% (w/v) carboxymethyl-β-CD, at a constant voltage of +25kV. DLLME was conducted using 2mL of liquid culture medium pH 9.5. Chloroform (100μL) and methanol (300μL) were employed as extraction and disperser solvent, respectively. After CE and DLLME optimization, the analytical method was fully validated. The method was linear over a concentration range of 90-6000ngmL(-1) for each ZO enantiomer (r>0.999) and 50-1000ngmL(-1) for each N-Des-ZO enantiomer (r>0.998). Absolute recovery of 51 and 82% was achieved for N-Des-ZO and ZO, respectively. The acc...Continue Reading

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Citations

Oct 6, 2015·Electrophoresis·Elena Sánchez-LópezAntonio L Crego
Dec 7, 2016·Electrophoresis·Ioannis J StavrouConstantina P Kapnissi-Christodoulou
May 14, 2019·Electrophoresis·Salvatore Fanali, Bezhan Chankvetadze
Feb 12, 2021·Electrophoresis·Jitka Caslavska, Wolfgang Thormann

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