کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1223189 967883 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice
چکیده انگلیسی

Sorafenib, a new oral multikinase inhibitor with antiangiogenic properties, has demonstrated preclinical and clinical activity against several tumor types. The aims of this study were to validate a method for the measurement of sorafenib in plasma from cancer patients, then to test this method in clinical practice. Following liquid–liquid extraction, the compounds were separated with gradient elution (on a C18 ultrasphere ODS column using a mobile phase of acetonitrile/20 mM ammonium acetate), then detected at 255 nm. The calibration was linear in the range 0.5–20 mg/L. Intra- and inter-assay precision was lower than 7 and 10%, respectively, at 0.5, 3 and 20 mg/L. Plasma sorafenib concentrations were measured in 22 cancer patients (99 samples). The mean trough sorafenib concentration (Cmin) and concentration at peak were 4.3 ± 2.5 mg/L (n = 68, CV = 57.5%) and 6.2 ± 3.0 mg/L (n = 31, CV = 47.5%), respectively. Mean sorafenib Cmin in eight patients who experienced grade 3 drug-related adverse events was approximately 1.5-fold greater than that observed in the remaining patients (7.7 ± 3.6 mg/L vs. 4.4 ± 2.4 mg/L, P = 0.0083). In conclusion, the method was successfully used in routine practice to monitor plasma concentrations of sorafenib in cancer patients. Finally, large interindividual variability and higher exposure in patients experiencing severe toxicity support the need for therapeutic drug monitoring to ensure an optimal exposure to sorafenib.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 49, Issue 4, 1 May 2009, Pages 1109–1114
نویسندگان
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