کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5509670 | 1538629 | 2017 | 33 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
An UPLC-MS/MS method for the quantification of BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (cobimetinib, trametinib, binimetinib) in human plasma. Application to treated melanoma patients
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کلمات کلیدی
MEKiLLOQESITQDEuropean Medical AgencyBRAFiLC-UVCminSPEEMAUPLCDabrafenibLC-MS/MS - LC-MS / MSMS/MS - MS / MSSolid phase extraction - استخراج فاز جامدTrough concentration - تمرکز بالاMelanoma - خال سرطانی یا ملانوماCoefficient of Variation - ضریب تغییرTandem mass spectrometry - طیف سنجی جرمی پشت سر هم یا متوالیBRAF inhibitors - مهار کننده های BRAFMEK inhibitors - مهار کننده های مجاهدین خلقtherapeutic drug monitoring - نظارت بر دارودرمانیVemurafenib - ومورفنیبPlasma - پلاسماTriple quadrupole - چهارگوش سه گانهultra performance liquid chromatography - کروماتوگرافی مایع با عملکرد فوق العادهquality control - کنترل کیفیتelectrospray ionization - یونیزاسیون الکترو اسپری
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Targeted therapies for cancers are fast-growing therapies. For instance kinase inhibitors such as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are increasingly used to treat malignant melanoma. The metabolic profile of these drugs can result in great interindividual variability, justifying therapeutic drug monitoring (TDM). We describe a rapid and specific method for quantification of 2 BRAFi (vemurafenib, dabrafenib) and 3 MEKi (cobimetinib, trametinib and binimetinib). Chromatography was performed on a Waters Acquity-UPLC system with CORTECS C18 + column, under a gradient of 10% acetic acid in water/acetonitrile. An Acquity-TQD® with electrospray ionization was used for detection. Samples were prepared by solid phase extraction (Oasis® MCX microElution) before injection in the system. Calibration curves ranges from 0.4 to 100 μg/ml for vemurafenib, from 1 to 1000 ng/ml for dabrafenib, from 0.5 to 500 ng/ml for cobimetinib and binimetinib, and from 0.75 to 250 ng/ml for trametinib. At all concentrations the bias was within ± 15% of the nominal concentrations and precision was â¤Â 15%. All results were within the acceptance criteria of the EMA guidelines on method validation. This rapid, sensitive and specific UPLC-MS/MS method can perform simultaneous quantification of targeted therapies used in malignant melanoma and is usable for routine TDM.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinica Chimica Acta - Volume 470, July 2017, Pages 8-13
Journal: Clinica Chimica Acta - Volume 470, July 2017, Pages 8-13
نویسندگان
Marine Rousset, Karine Titier, Stephane Bouchet, Caroline Dutriaux, Anne Pham-Ledard, Sorilla Prey, Mireille Canal-Raffin, Mathieu Molimard,