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Development and validation of a LC-MS/MS method for in vivo quantification of meta-iodobenzylguanidine (mIBG).
López Quiñones, Antonio J; Shireman, Laura M; Wang, Joanne.
Afiliación
  • López Quiñones AJ; Department of Pharmaceutics, University of Washington, Seattle WA 98195, United States.
  • Shireman LM; Department of Pharmaceutics, University of Washington, Seattle WA 98195, United States.
  • Wang J; Department of Pharmaceutics, University of Washington, Seattle WA 98195, United States. Electronic address: jowang@uw.edu.
Article en En | MEDLINE | ID: mdl-34530306
meta-iodobenzylguanidine (mIBG) is a radiopharmaceutical used for the diagnosis and treatment of neuroendocrine cancers. Previous quantification of mIBG in biodistribution and pharmacokinetic studies mainly relied on the use of radiolabeled mIBG, which involves the handling of highly radioactive materials. The goal of this study was to develop a nonradioactive analytical method for quantifying mIBG in mouse plasma and tissue homogenates using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples were prepared for analysis using a protein precipitation method. Mass spectrometry analysis was performed using 4-hydroxyphenformin as the internal standard, and the mass-to-charge transitions were 276.1 → 217.0 for mIBG and 222.1 → 121.0 for 4-hydroxyphenformin. The quantification limit of mIBG was 0.98 ng/mL, and the method was linear up to 500 ng/mL. The accuracy, inter-day and intra-day precision were 96-112%, 5.5-14.4%, and 3.7-14.1%, respectively, suggesting that the method was accurate and precise in quantifying mIBG at multiple concentrations in mouse plasma and liver homogenates. The extraction recovery was 96-106% and the matrix effect was 95-110%, indicating that the method was reproducible in quantifying mIBG with minimal impact from the biological matrices. In summary, we have developed and validated a fast, high-throughput quantification method of non-radiolabeled mIBG using LC-MS/MS. This method is reproducible, accurate, and precise, and can be used to quantify mIBG in plasma and tissue matrices to determine the pharmacokinetics and biodistribution of mIBG in preclinical animal models.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / 3-Yodobencilguanidina / Espectrometría de Masas en Tándem Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Chromatogr B Analyt Technol Biomed Life Sci Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / 3-Yodobencilguanidina / Espectrometría de Masas en Tándem Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Chromatogr B Analyt Technol Biomed Life Sci Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos