Simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and LC-MS: application to pharmacokinetic study

A sensitive and selective liquid chromatography–mass spectrometry (LC–MS) method for determination of midazolam and its metabolite 1’-hydroxymidazolam in rat plasma was developed and validated. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile was used...

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Autores principales: Chen, Xiaole, Xu, Tao, Wang, Zhe, Pan, Peipei, Luo, Shunbing, Lin, Dan, Hu, Guoxin, Pan, Jianchun
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/20174
http://www.latamjpharm.org/resumenes/31/4/LAJOP_31_4_1_6.pdf
Aporte de:
id I19-R120-10915-20174
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Farmacia
1’-hydroxymidazolam
LC–MS
Midazolam
Plasma
Espectrometría de Masas
Farmacocinética
spellingShingle Farmacia
1’-hydroxymidazolam
LC–MS
Midazolam
Plasma
Espectrometría de Masas
Farmacocinética
Chen, Xiaole
Xu, Tao
Wang, Zhe
Pan, Peipei
Luo, Shunbing
Lin, Dan
Hu, Guoxin
Pan, Jianchun
Simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and LC-MS: application to pharmacokinetic study
topic_facet Farmacia
1’-hydroxymidazolam
LC–MS
Midazolam
Plasma
Espectrometría de Masas
Farmacocinética
description A sensitive and selective liquid chromatography–mass spectrometry (LC–MS) method for determination of midazolam and its metabolite 1’-hydroxymidazolam in rat plasma was developed and validated. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. The chromatographic separation was performed on a Zorbax SB-C18 column (150 × 2.1 mm, 5 μm), using acetonitrile-0.1 % formic acid as the mobile phase with gradient elution, delivered at a flow-rate of 0.4 mL/min. Electrospray ionization (ESI) source was applied and operated in positive ion mode, and selected ion monitoring (SIM) mode used to quantify midazolam and its metabolite 1’- hydroxymidazolam. Calibration curves were linear in the concentration ranges of 5-2000 ng/mL for midazolam and 10-2000 ng/mL for 1’-hydroxymidazolam, with a lower limit of quantification (LLOQ) of 5 ng/mL for midazolam and 10 ng/mL for 1’-hydroxymidazolam, respectively. Intra- and inter-day precision were less than 13 % and the accuracy ranged from -10.7 to 9.5 %. This developed method was successfully used for determination of midazolam and its metabolite 1’-hydroxymidazolam in rat plasma for pharmacokinetic study.
format Articulo
Articulo
author Chen, Xiaole
Xu, Tao
Wang, Zhe
Pan, Peipei
Luo, Shunbing
Lin, Dan
Hu, Guoxin
Pan, Jianchun
author_facet Chen, Xiaole
Xu, Tao
Wang, Zhe
Pan, Peipei
Luo, Shunbing
Lin, Dan
Hu, Guoxin
Pan, Jianchun
author_sort Chen, Xiaole
title Simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and LC-MS: application to pharmacokinetic study
title_short Simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and LC-MS: application to pharmacokinetic study
title_full Simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and LC-MS: application to pharmacokinetic study
title_fullStr Simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and LC-MS: application to pharmacokinetic study
title_full_unstemmed Simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and LC-MS: application to pharmacokinetic study
title_sort simultaneous determination of midazolam and 1’-hydroxymidazolam in rat plasma by protein precipitation and lc-ms: application to pharmacokinetic study
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/20174
http://www.latamjpharm.org/resumenes/31/4/LAJOP_31_4_1_6.pdf
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