کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7626837 | 1494583 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Development and validation of a high-performance liquid chromatography method for the quantitation of intracellular PARP inhibitor Olaparib in cancer cells
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Olaparib is a potent PARP inhibitor in clinical use for cancer therapy. A bioanalytical assay was developed and validated for quantitation of intracellular level of olaparib in cells exposed to the drug. The assay involves an optimized and straightforward sample pretreatment with acetonitrile for olaparib solubilization, cell lysis and protein precipitation, and a high performance liquid chromatography (HPLC) method with ultraviolet detection. Several parameters in both the sample preparation and the detection steps were investigated. Optimal chromatographic conditions were achieved with a 5â¯Î¼L injection on a Nova-Pak® C18 column (150â¯Ãâ¯3.9â¯mm, 4â¯Î¼m) using a mobile phase consisting of acetonitrile and ultra-pure water in gradient mode, at a constant 1.2â¯mL/min flow rate, at 35â¯Â°C. Detection was carried out at 254â¯nm and a diode array detector was used to insure purity of the olaparib peak. The method was validated according to Food and Drug Administration guidelines. Linearity, accuracy and precisions were satisfactory over the concentration range of 200-2000â¯ng/mL. Limits of detection and quantification for olaparib were 50â¯ng/mL and 200â¯ng/mL, respectively. Good stability was showed in three relevant analytical conditions. Finally, the validated analytical method was successfully used to estimate the intracellular level of olaparib in SUM1315 breast cancer cells. A significant difference was observed in intracellular drug level after 1 and 3â¯h incubations. This method permitting measurement of drug level in tumor cells would allow dosage optimization and improvement of treatment response predictions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 152, 15 April 2018, Pages 74-80
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 152, 15 April 2018, Pages 74-80
نویسندگان
Pierre Daumar, Robin Dufour, Clémence Dubois, Frédérique Penault-Llorca, Mahchid Bamdad, Emmanuelle Mounetou,