• International journal of thyroidology
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• v.11 no.2
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• pp.61-70
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• 2018

Tyrosine kinase inhibitors (TKIs) are widely used for the treatment of advanced radioiodine-refractory thyroid cancer. Although the previous studies including large-scale randomized controlled trials have demonstrated the effects of TKIs in advanced thyroid cancers, it has been found that most patients experienced adverse events (AEs). Unlike other cancers, even patients with advanced thyroid cancers are often asymptomatic. Rather, TKI use can make patients suffer adverse events. Therefore, the use of TKI should be decided after the full consideration of AEs as well as its efficacies. While using TKI, AEs should be monitored, evaluated, and managed appropriately, if AEs develop. In this review, the occurrence, evaluation, and management of AEs of sorafenib, lenvatinib, and vandetanib will be described, which TKIs are most commonly used for the treatment of advanced thyroid cancer. Some suggestions for the management of AEs in the real life are also provided.

• Journal of Life Science
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• v.22 no.11
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• pp.1456-1462
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• 2012

Sorafenib is a multikinase inhibitor and an oral anticancer drug approved for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. The purpose of this study was to develop an efficient method of the determination of sorafenib in human plasma using tandem mass spectrometry coupled with liquid chromatography (LC/MS/MS) and validate the method by the guidelines of the Korean Food and Drug Administration (KFDA). Plasma samples ($100{\mu}l$) were added with chlorantraniliprole as an internal standard and then mixed with the 0.1% formic acid-containing extraction solution composed of isopropyl alcohol and ethyl acetate (1:4, v/v). After centrifugation, the supernatant was concentrated at $45^{\circ}C$ under negative pressure and centrifugal force. The residue was reconstituted with a mobile phase and injected into the HPLC instrument using a reverse phase Waters XTerra$^{TM}$ C18 column (particle size $3.5{\mu}m$). Liquid chromatography was carried out within the run time of 5 min using a mobile phase composed of buffer (0.1% formic acid and 10 mM ammonium formate), methanol, and acetonitrile (1:6:3, v/v/v). The analytes were monitored by tandem mass spectrometry in the multiple reaction monitoring method programmed to detect sorafenib at 'm/z 465.2 ${\rightarrow}$ 252.5' and chlorantraniliprole at 'm/z 484.4 ${\rightarrow}$ 286.2' with positive electrospray ionization mode ($ES^+$). The result showed the proper linearity ($r^2$ > 0.99) over the range of 2,000-5,000 ng/ml with good accuracy (90.7-103.9%) and precision (less than 10%). The newly developed method using LC/MS/MS was validated by the guideline of KFDA and identified as more sensitive compared to the previous methods.