Development and validation of high-performance liquid chromatography-tandem mass spectrometry assay for 6-(3-benzoyl-ureido)-hexanoic acid hydroxyamide, a novel HDAC inhibitor, in mouse plasma for pharmacokinetic studies.
Biomed Chromatogr
; 21(2): 184-9, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17221921
A liquid chromatography/tandem mass spectrometric method for the quantification of 6-(3-benzoyl-ureido)-hexanoic acid hydroxyamide (EX-2), a novel histone deacetylase (HDAC) inhibitor, in mouse plasma was developed to support in-house pharmacokinetic (PK) studies in the lead optimization stage. In order to determine the PK parameters for EX-2 in comparison to other HDAC inhibitors such as suberoylanilide hydroxamic acid (SAHA), PXD-101 and LBH-589, which are currently in different stages of clinical trials, research-grade bio-analytical method validations were carried out for EX-2 and these reference HDAC inhibitors, which were synthesized by in-house medicinal chemists. The components of validation consisted of specificity, extraction efficiency, signal-response of calibration standards, lower limit of quantification, autosampler stability and accuracy and precision of quality control samples. The validated LC/MS/MS methods were accurate and precise. The calibration curve ranged from 1 to 1600 ng/mL for all the analytes. The methods developed were used to quantify EX-2 and other HDAC inhibitors in mouse plasma obtained from pharmacokinetic studies. The results suggest that EX-2 has better PK parameters compared with the reference drugs and is a promising drug development candidate.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromatografía Líquida de Alta Presión
/
Espectrometría de Masas en Tándem
/
Inhibidores de Histona Desacetilasas
/
Ácidos Hidroxámicos
Tipo de estudio:
Guideline
Límite:
Animals
Idioma:
En
Revista:
Biomed Chromatogr
Año:
2007
Tipo del documento:
Article
Pais de publicación:
Reino Unido