Desenvolvimento e validação de técnica bioanalítica em LC-MS/MS para detecção e quantificação de protótipos antineoplásticos
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Data
2014-11-05
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Universidade Federal de Goiás
Resumo
A rapid, sensitive and selective liquid chromatography tandem mass spectrometry
(LC/MS-MS) bioanalytical method was developed and validated to quantify LQFM018
and LQFM030 prototypes obtained by molecular simplification nutlins (inhibitors of
MDM2-p53 interaction) in mouse, rat and human plasma. The prototypes and the
internal standard domperidone were extracted from the plasma samples by liquid-liquid
extraction using methyl tert-butyl ether. The chromatographic analysis was performed
using ACE ® C18 analytical column (5µm 100 x 4.6 mm) for a total time of 4 minutes. In
MRM method transitions (m/z) were used: 349.138/191.10, 319.162/191.20 and
426.032/175.20 Daltons to LQFM018; LQFM030 and internal standard, respectively.
The mobile phase consists of methanol-2 mM ammonium acetate containing 0.025%
formic acid. The calibration curve was linear over the concentration range examined 10-
15000 ng/mL with r> 0.99 and the limit of quantitation of 10 ng/mL for both prototypes.
For LQFM018, intra-assay precision was 0.8 to 7.3% and accuracy from 96.8 to 105.8%.
And inter-assay to the precision was 2.3 and 6.6% and accuracy was 99.3 to 104.3%.
The average recovery was 65.0% and the matrix effect between -11.2 to 2.1%. To
LQFM030, intra-assay precision was 0.6 to 5.5% and accuracy from 95.5 to 111.3%.
Inter-assay precision was 1.8 to 6.7%, and accuracy was 99.0 to 107.0%. The average
recovery was 74.1% and the matrix effect from -7.9 to 1.5%. Recovery for internal
standard was 61.3%. The prototypes were considered stable in the biological matrix and
the solution proposed tests. Thus, the analytical method was developed and validated is
capable to quantify traces of concentration in plasma.
Descrição
Palavras-chave
LC-MS/MS , LQFM018 , LQFM030 , Nutlins , Inibidores de MDM2-p53 , Antitumorais , LC-MS/MS , LQFM018 , LQFM030 , Nutlins , Inhibitors of MDM2-p53 , Antitumors
Citação
GOMES, S. A. Desenvolvimento e validação de técnica bioanalítica em LC-MS/MS para detecção e quantificação de protótipos antineoplásticos. 2014. 86 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2014.