Development and validation of a simple and sensitive high-resolution LC/MS method for determination of PF-04620110 in dog plasma: Application to a pharmacokinetic study.
Biomed Chromatogr
; 33(9): e4562, 2019 Sep.
Article
en En
| MEDLINE
| ID: mdl-31017300
ABSTRACT
In this study, a more sensitive and reliable quantitative method based on ultra-high performance liquid chromatography coupled with Q-Exactive-Orbitrap-MS in full-mass scan was developed and validated for the determination of PF-04620110 in dog plasma. After protein precipitation with acetonitrile, the sample separations were carried out on an Acquity BEH C18 column with 1 mm ammonium acetate in water and acetonitrile containing 0.1% acetic acid as mobile phase, at a flow rate of 0.4 mL/min. The assay showed excellent linearity over the concentration range of 1-2000 ng/mL with correlation coefficient >0.9980 (r > 0.9980). The LLOQ was 1 ng/mL. The inter- and intra-day precision (RSD, %) was within 9.69% while the accuracy (RE, %) was in the range of -8.59-11.24%. The extraction recovery was >85.37% and the assay was free of matrix effects. PF-04620110 was demonstrated to be stable under various processing and handing conditions. The validated method was successfully applied to the pharmacokinetic study of PF-04620110 in dogs and the results revealed that PF-04620110 was slowly eliminated from plasma with a clearance of 60.81 ± 7.11 mL/h/kg for intravenous administration and 81.44 ± 25.79 mL/h/kg for oral administration. The oral bioavailability was determined to be 77.89% in dogs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxazepinas
/
Cromatografía Líquida de Alta Presión
/
Espectrometría de Masas en Tándem
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Chromatogr
Año:
2019
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM