Identification and characterization of vilazodone metabolites in rats and microsomes by ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry.
Rapid Commun Mass Spectrom
; 31(23): 1974-1984, 2017 Dec 15.
Article
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| MEDLINE
| ID: mdl-28875544
RATIONALE: Vilazodone is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of major depressive disorder (MDD). An extensive literature search found few reports on the in vivo and in vitro metabolism of vilazodone. Therefore, we report a comprehensive in vivo and in vitro metabolic identification and structural characterization of vilazodone using ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF/MS/MS) and in silico toxicity study of the metabolites. METHODS: To identify in vivo metabolites of vilazodone, blood, urine and faeces samples were collected at different time intervals starting from 0 h to 48 h after oral administration of vilazodone to Sprague-Dawley rats. The in vitro metabolism study was conducted with human liver microsomes (HLM) and rat liver microsomes (RLM). The samples were prepared using an optimized sample preparation approach involving protein precipitation followed by solid-phase extraction. The metabolites have been identified and characterized by using LC/ESI-MS/MS. RESULTS: A total of 12 metabolites (M1-M12) were identified in in vivo and in vitro matrices and characterized by LC/ESI-MS/MS. The majority of the metabolites were observed in urine, while a few metabolites were present in faeces and plasma. Two metabolites were observed in the in vitro study. A semi-quantitative study based on percentage counts shows that metabolites M11, M6 and M8 were observed in higher amounts in urine, faeces and plasma, respectively. CONCLUSIONS: The structures of all the 12 metabolites were elucidated by using LC/ESI-MS/MS. The study suggests that vilazodone was metabolized via hydroxylation, dihydroxylation, glucuronidation, oxidative deamination, dealkylation, dehydrogenation and dioxidation. All the metabolites were screened for toxicity using an in silico tool.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microsomas Hepáticos
/
Inhibidores Selectivos de la Recaptación de Serotonina
/
Clorhidrato de Vilazodona
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Rapid Commun Mass Spectrom
Año:
2017
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Reino Unido