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Ultra-sensitive LC-MS/MS method for the quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine in human plasma for a microdose clinical trial.
van Nuland, M; Hillebrand, M J X; Rosing, H; Burgers, J A; Schellens, J H M; Beijnen, J H.
Afiliación
  • van Nuland M; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The N
  • Hillebrand MJX; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands.
  • Rosing H; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands.
  • Burgers JA; Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Schellens JHM; Division of Clinical Pharmacology, Department of Medical Oncology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht,
  • Beijnen JH; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The N
J Pharm Biomed Anal ; 151: 25-31, 2018 Mar 20.
Article en En | MEDLINE | ID: mdl-29294409
In microdose clinical trials a maximum of 100 µg of drug substance is administered to participants, in order to determine the pharmacokinetic properties of the agents. Measuring low plasma concentrations after administration of a microdose is challenging and requires the use of ulta-sensitive equipment. Novel liquid chromatography-mass spectrometry (LC-MS/MS) platforms can be used for quantification of low drug plasma levels. Here we describe the development and validation of an LC-MS/MS method for quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in the low picogram per milliliter range to support a microdose trial. The validated assay ranges from 2.5-500 pg/mL for gemcitabine and 250-50,000 pg/mL for dFdU were linear, with a correlation coefficient (r2) of 0.996 or better. Sample preparation with solid phase extraction provided a good and reproducible recovery. All results were within the acceptance criteria of the latest US FDA guidance and EMA guidelines. In addition, the method was successfully applied to measure plasma concentrations of gemcitabine in a patient after administration of a microdose of gemcitabine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos Clínicos Fase I como Asunto / Floxuridina / Desoxicitidina / Espectrometría de Masas en Tándem Tipo de estudio: Diagnostic_studies / Guideline Límite: Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos Clínicos Fase I como Asunto / Floxuridina / Desoxicitidina / Espectrometría de Masas en Tándem Tipo de estudio: Diagnostic_studies / Guideline Límite: Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido