Oligonucleotide quantification and metabolite profiling by high-resolution and accurate mass spectrometry.
Bioanalysis
; 11(21): 1967-1980, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31829056
ABSTRACT
Aim:
Advancements in RNA interference therapeutics have triggered development of improved bioanalytical methods for oligonucleotide metabolite profiling and high-throughput quantification in biological matrices. Results &methodology:
HPLC coupled with high-resolution mass spectrometry (LC-HRMS) methods were developed to investigate the metabolism of a REVERSIR™ molecule in vivo. Plasma and tissue samples were extracted using solid-phase extraction followed by LC-HRMS analysis for metabolite profiling and quantification. The method was qualified from 10 to 5000 ng/ml (plasma) and 100 to 50000 ng/g (liver and kidney). In rat liver, intra and interday accuracy ranged from 80.9 to 118.5% and 88.4 to 111.9%, respectively, with acceptable precision (<20% CV).Conclusion:
The LC-HRMS method can be applied for metabolite profiling and quantification of oligonucleotides in biological matrices.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Espectrometria de Massas
/
Metabolômica
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article