Practical approaches to incurred sample LC-MS/MS reanalysis: confirming unexpected results.
Anal Chem
; 85(4): 2405-13, 2013 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-23363493
ABSTRACT
Incurred sample reanalysis (ISR) is an important step in assuring the quality of an LC-MS/MS bioanalytical assay and the integrity of bioanalysis conduct. A conventional ISR involves analysis of at least 20 samples taken from an in vivo study a second time using the method that was described in prestudy validation and employed in generating the initial study sample results. However, this practice is sometimes inadequate to confirm bioanalytical results that are unexpected. The present report discusses several additional exploratory activities that were performed to confirm the unexpected plasma concentration-time results of NVP-1, an investigational drug candidate, observed in the plasma samples collected from patients in a phase II trial. These approaches include (1) LC-MS/MS reanalysis of the study samples after multiple freeze/thaw cycles followed by a short-term benchtop storage, (2) evaluation of additional MS/MS transitions in LC-MS/MS, (3) employment of a different sample preparation procedure in LC-MS/MS, and (4) study sample dilution using plasma samples from healthy volunteers. These procedures are practical and can be readily implemented in the confirmatory LC-MS/MS bioanalysis of other small molecules.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida de Alta Pressão
/
Inibidores Enzimáticos
/
Espectrometria de Massas em Tandem
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article