کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1221525 1494638 2014 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A LC/MS/MS micro-method for human plasma quantification of vemurafenib. Application to treated melanoma patients
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
A LC/MS/MS micro-method for human plasma quantification of vemurafenib. Application to treated melanoma patients
چکیده انگلیسی


• Method allowing quantification of plasma vemurafenib with only 10-μL samples.
• A simple precipitation is needed.
• High variability of plasma vemurafenib concentrations with recommended doses.
• Similar plasma concentrations at Cmax and Cmin at steady state.
• High dose needed in some patients to achieve “usual concentrations”.

As previously shown for imatinib, therapeutic drug monitoring (TDM) of vemurafenib should be important to measure efficacy of the treatment in melanoma patient. A micro-method based on liquid chromatography coupled to triple quadrupole spectrometry detection using only 10 μL of plasma was validated. A simple protein precipitation with water/acetonitrile was used after addition of vemurafenib-13C6 as internal standard. The ion transitions used to monitor analytes were m/z 490.2 → m/z 255.2 and m/z 383.3 for vemurafenib and m/z 496.2 → m/z 261.2 and m/z 389.3 for vemurafenib-13C6. Calibration curves were linear in the 0.1–100 μg/mL range, the limits of detection and quantification being 0.01 μg/mL and 0.1 μg/mL, respectively. The intra- and inter-assay precisions evaluated at 0.1, 0.3, 15, 45 and 80 μg/mL were lower than 13.3% and the accuracies were in the 93.7–105.8 range. No matrix effect was observed. At steady state, the results of TDM of vemurafenib in 26 patients treated by 960 mg twice daily (n = 60 samples), 13 patients with 740 mg twice daily (n = 13) and one with 1200 mg twice daily (n = 3) showed a great variability of the pharmacokinetics of this compound.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 97, 25 August 2014, Pages 29–32
نویسندگان
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