کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1217126 967068 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development of a quantification method for digoxin, a typical P-glycoprotein probe in clinical and non-clinical studies, using high performance liquid chromatography–tandem mass spectrometry: The usefulness of negative ionization mode to avoid competitive
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Development of a quantification method for digoxin, a typical P-glycoprotein probe in clinical and non-clinical studies, using high performance liquid chromatography–tandem mass spectrometry: The usefulness of negative ionization mode to avoid competitive
چکیده انگلیسی

Highly sensitive and accurate liquid chromatography–tandem mass spectrometry (LC/MS/MS) methods have been developed and validated for measuring digoxin (DGX), a typical P-glycoprotein probe, in human plasma, rat plasma, and rat brain. We extracted DGX and deuterium-labeled DGX (as internal standard) from sample fluids under basic conditions using acetonitrile and sodium chloride-saturated 0.1 mol/L sodium hydroxide. The upper organic layer was diluted with distilled water, and the resulting solution was injected into an LC/MS/MS system in negative ionization mode. Chromatographic separation was achieved on a C18-ODS column in the gradient mobile phase, which comprised 0.05% (w/v) ammonium carbonate (pH 9.0) and methanol at a flow rate of 0.7 mL/min. Regardless of the type of biological matrix, intra-day and inter-day validation tests demonstrated good linearity of calibration curves within ranges of 0.1–10 ng/mL for plasma and 0.5–50 ng/g for rat brain and gave excellent accuracy and precision of quality control samples at 4 concentration levels. Unlike existing methods, our approach uses negative ionization to avoid competitive adduct formation of DGX. Our method showed higher sensitivity and wider applicability to various types of biological matrices than existing methods. Our method will support clinical and preclinical investigation of in vivo P-glycoprotein functionality using DGX.


► Highly sensitive and accurate LC/MS/MS method was developed for measuring digoxin.
► The developed method achieved higher sensitivity than previously reported methods requiring only 25 μL of the sample fluid.
► The key successful factor was to employ negative ionization to completely avoid competitive adduct formation.
► The unique, one-step sample pretreatment method may provide advantages over existing methods, such as the small required sample volume, no need for extensive sample cleanup, safety, and low cost of the procedure, among others.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 879, Issue 32, 15 December 2011, Pages 3837–3844
نویسندگان
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