Enantioselective analysis of zopiclone and its metabolites in plasma by liquid chromatography/tandem mass spectrometry


Autoria(s): TONON, Milena Araujo; JABOR, Valquiria A. P.; BONATO, Pierina Sueli
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2011

Resumo

A high-performance liquid chromatographic method with triple-quadrupole mass spectrometry detection (LC-MS-MS) was developed and validated for the first time for the simultaneous quantification of zopiclone and its metabolites in rat plasma samples. The analytes were isolated from rat plasma by liquid-liquid extraction and separated using a chiral stationary phase based on an amylose derivative, Chiralpak ADR-H column, and ethanol-methanol-acetonitrile (50:45:5, v/v/v) plus 0.025% diethylamine as the mobile phase, at a flow-rate of 1.0 mL min(-1). Moclobemide was used as the internal standard. The developed method was linear over the concentration range of 7.5-500 ng mL(-1). The mean absolute recoveries were 74.6 and 75.7; 61.6 and 56.9; 72.5, and 70.7 for zopiclone enantiomers, for N-desmethyl zopiclone enantiomers and for zopiclone-N-oxide enantiomers, respectively, and 75.9 for the internal standard. Precision and accuracy were within acceptable levels of confidence (<15%). The method application in a pilot study of zopiclone kinetic disposition in rats showed that the levels of (+)-(S)-zopiclone were always higher than those of (-)-R-zopiclone. Higher concentrations were also observed for (+)-(S)-N-desmethyl zopiclone and (+)-(S)-N-oxide zopiclone, confirming the stereoselective disposition of zopiclone.

CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo

Identificador

ANALYTICAL AND BIOANALYTICAL CHEMISTRY, v.400, n.10, p.3517-3525, 2011

1618-2642

http://producao.usp.br/handle/BDPI/19947

10.1007/s00216-011-5033-0

http://dx.doi.org/10.1007/s00216-011-5033-0

Idioma(s)

eng

Publicador

SPRINGER HEIDELBERG

Relação

Analytical and Bioanalytical Chemistry

Direitos

restrictedAccess

Copyright SPRINGER HEIDELBERG

Palavras-Chave #Zopiclone #LC-MS-MS #Metabolites #Kinetic disposition #ENANTIOMERS #DEGRADATION #URINE #Biochemical Research Methods #Chemistry, Analytical
Tipo

article

original article

publishedVersion