Assessment of pharmacokinetics, bioavailability and protein binding of anacetrapib in rats by a simple high-performance liquid chromatography-tandem mass spectrometry method.
Biomed Chromatogr
; 31(2)2017 Feb.
Article
em En
| MEDLINE
| ID: mdl-27432781
ABSTRACT
Anacetrapib is a potent and selective CETP inhibitor and is undergoing phase III clinical trials for the treatment of dyslipidemia. A simple and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of anacetrapib in rat plasma was developed and validated using an easily purchasable compound, chlorpropamide, as an internal standard (IS). A minimal volume of rat plasma sample (20 µL) was prepared by a single-step deproteinization procedure with 80 µL of acetonitrile. Chromatographic separation was performed using Kinetex C18 column with a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid at a flow rate of 0.3 mL/min. Mass spectrometric detection was performed using selected reaction monitoring modes at the mass/charge transitions m/z 638 â 283 for anacetrapib and m/z 277 â 175 for IS. The assay was validated to demonstrate the selectivity, linearity, precision, accuracy, recovery, matrix effect and stability. The lower limit of quantification was 5 ng/mL. This LC-MS/MS assay was successfully applied in the rat plasma protein binding and pharmacokinetic studies of anacetrapib. The fraction of unbound anacetrapib was determined to be low (ranging from 5.66 to 12.3%), and the absolute oral bioavailability of anacetrapib was 32.7%.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida de Alta Pressão
/
Oxazolidinonas
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Espectrometria de Massas em Tandem
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Anticolesterolemiantes
Limite:
Animals
Idioma:
En
Revista:
Biomed Chromatogr
Ano de publicação:
2017
Tipo de documento:
Article