Liquid chromatography-mass spectrometry methods for the intracellular determination of drugs and their metabolites: a focus on antiviral drugs.
Anal Bioanal Chem
; 409(25): 5837-5853, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28707063
ABSTRACT
Understanding the efficacy and/or toxicity of most drugs requires effective intracellular measurements of the drug and its metabolites. Nevertheless, the most common plasma marker of the biological effect of the drug is the area under the curve. Compared with drug determination in whole blood or urine, various difficulties occur in the development of analytical methods for intracellular measurements. We propose step-by-step guidelines to develop an analytical method exploring intracellular concentrations of antivirals and/or their metabolites. These guidelines are illustrated with the most sensitive liquid chromatography-mass spectrometry methods developed for human in vivo and in vitro studies. We summarize 18 studies that provided methods to explore intracellular concentrations of antivirals since 2002. To explore intracellular metabolites, two different approaches can be envisaged. The direct approach, most frequently using ion-pairing agents, is fast and requires only a small sample but is expensive. The indirect approach is the more widely used approach, but is cumbersome and time-consuming. In both cases, liquid chromatography-mass spectrometry has become the method of choice to determine intracellular drug concentrations with high sensitivity. These methods may increase our understanding of drug behavior in organisms. This is true for preclinical studies where the mechanism of action, the metabolism, and the toxicity of drugs are explored. It is also true for clinical applications when dose adjustment is needed and cannot rely on blood concentrations. Graphical Abstract Direct and indirect approaches to measure intracellular concentrations.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Espectrometria de Massas
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Cromatografia Líquida
Tipo de estudo:
Guideline
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article