کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7626952 1494584 2018 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
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
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
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
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 151, 20 March 2018, Pages 25-31
نویسندگان
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