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A novel LC-MS/MS method for simultaneous estimation of acalabrutinib and its active metabolite acalabrutinib M(27) in human plasma and application to a human pharmacokinetic study

A simple, specific, selective and accurate bioanalytical method was developed and validated for simultaneous estimation of acalabrutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Deuterated analogs of both the analytes were used as int...

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Detalles Bibliográficos
Autores principales: Valluri, Venkat Rao, Katari, Naresh Kumar, Khatri, Chirag, Kasar, Pankaj, Polagani, Srinivasa Rao, Jonnalagadda, Sreekanth Babu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982068/
https://www.ncbi.nlm.nih.gov/pubmed/35424612
http://dx.doi.org/10.1039/d1ra09026g
Descripción
Sumario:A simple, specific, selective and accurate bioanalytical method was developed and validated for simultaneous estimation of acalabrutinib and its active metabolite in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Deuterated analogs of both the analytes were used as internal standards. The extraction of analytes and internal standards were evaluated from the human plasma by liquid–liquid extraction technique using methyl tertiary butyl ether (TBME). The separation of the analytes was carried out on Zorbax Eclipse XDB-C(18 ()150 × 4.6 mm, 5 μm) column with a mixture of acetonitrile and 10 mM ammonium formate in 0.1% formic acid buffer (65 : 35, v/v) as mobile phase at a flow rate of 1 mL min(−1). The method linearity was determined in the widen concentration range from 5.000 ng mL(−1) to 1600 ng mL(−1) with r(2) > 0.99. The entire method validation was carried out as per the USFDA guidelines on bioanalytical method validation and all validation experiment results were found within acceptable limits. Clinical pharmacokinetic study of both the parent drug and its active metabolite was successfully performed on six healthy volunteers under fasting conditions by applying the present method.