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Un método cuantitativo de interacción hidrófila UPLC-MS/MS para la cuantificación de saracatinib en la matriz de

Mohamed W Attwa¹, Adnan A Kadi¹

¹Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. mzeidan@ksu.edu.sa.

Analytical methods : advancing methods and applications

|February 11, 2026

Resumen

Este estudio desarrolló un método rápido UPLC-MS/MS para medir el saracatinib (SRB) en los microsomas hepáticos, revelando su estabilidad metabólica. El análisis in silico sugiere que las modificaciones estructurales podrían mejorar el SRB.

Área de la Ciencia:

Farmacología y Toxicología.
Química Analítica La Química Analítica es la
Metabolismo de las drogas Metabolismo de las drogas

Sus antecedentes:

Saracatinib (SRB) es un inhibidor de la doble quinasa bajo investigación clínica.
No se han informado estudios previos sobre la estabilidad metabólica de SRB.
Comprender el metabolismo de SRB es crucial para su desarrollo clínico.

Objetivo del estudio:

Desarrollar y validar un método ultra-rápido, ecológico y sensible UPLC-MS/MS para la cuantificación de SRB en microsomas hepáticos humanos (HLM).
Para evaluar la estabilidad metabólica de SRB en HLMs.
Para predecir las responsabilidades metabólicas potenciales y la toxicidad de SRB utilizando herramientas in silico.

Principales métodos:

Desarrollo de un método UPLC-MS/MS utilizando una columna Luna HILIC y una fase móvil a base de acetonitrilo.
Cuantificación de SRB en HLMs a través de la precipitación de proteínas con acetonitrilo.
Validación del método bioanalítico de acuerdo con las directrices de la FDA.
Análisis in silico de la estructura de SRB para la predicción metabólica y de toxicidad.

Principales resultados:

Se estableció un método validado UPLC-MS/MS con un tiempo de ejecución de 1,0 minuto y un rango lineal de 1-4000 ng/mL.
SRB exhibió una vida media in vitro (t1/2) de 17.24 min y un aclaramiento intrínseco (Clint) de 47.02 mL/min/kg.
Las predicciones in silico sugirieron que modificar el anillo de N-metil piperazina podría mejorar la estabilidad metabólica y la seguridad de SRB.

Conclusiones:

El método UPLC-MS/MS desarrollado es adecuado para cuantificar la SRB en HLMs, apoyando estudios de metabolismo de fármacos.
SRB demuestra una estabilidad metabólica moderada en los microsomas hepáticos humanos.
El modelado in silico proporciona información valiosa para optimizar la estructura de SRB para mejorar su perfil farmacocinético y seguridad.

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