Quantification of raf antisense oligonucleotide (rafAON) in biological matrices by LC-MS/MS to support pharmacokinetics of a liposome-entrapped rafAON formulation.
Biomed Chromatogr
; 19(4): 272-8, 2005 May.
Article
en En
| MEDLINE
| ID: mdl-15627279
ABSTRACT
An LC-MS/MS method was developed to quantify an antisense oligonucleotide against Raf-1 expression (rafAON) in monkey and mouse plasma and in mouse tissue homogenates from animals dosed with a liposome-entrapped rafAON easy-to-use formulation (LErafAON-ETU) intended for use as an antineoplastic agent. RafAON was extracted from mouse and monkey plasma using solid-phase extraction. Tissues were homogenized and sample cleanup was achieved by protein precipitation. RafAON and the internal standard (IS) were separated on a Hamilton PRP-1 column and quantified by tandem mass spectrometry using an electrospray source in negative ion mode. The total run time was 4.0 min. The peak areas of two rafAON transitions were summed and plotted against the peak area of an IS transition to generate the standard curve. In monkey plasma the linear range was 50-10,000 ng/mL, and in mouse plasma it was 25-5000 ng/mL. The lower limit of quantification was 500 ng/mL (10 microg/g tissue) in heart, kidney, liver, lung and spleen homogenates, and the standard curve was linear up to 10,000 ng/mL. Accuracy, precision and stability were evaluated and found to be acceptable in all three matrices. The assay was used to support pharmacokinetics and tissue distribution studies of LErafAON-ETU in mice and monkeys.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligodesoxirribonucleótidos
/
Cromatografía Liquida
/
Proteínas Proto-Oncogénicas c-raf
/
Oligodesoxirribonucleótidos Antisentido
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Chromatogr
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos