Stanovení celkového sunitinibu pomocí kapalinové chromatografie s tandemovou hmotnostní spektrometrií
| Title in English | Determination of total sunitinib by tandem mass spectrometry liquid chromatography |
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| Year of publication | 2018 |
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| Citation | |
| Description | Sunitinib (SUN) has been an approved cytotoxic agent since 2006 for the treatment of patients with advanced and / or metastatic renal carcinoma (mRCC), gastrointestinal stromal tumors (GIST) and pancreatic neuroendocrine tumors (pNET). It belongs among tyrosine kinase inhibitors targeting several receptors, but its use often leads to undesirable effects, eg hand-foot syndrome, stomatitis, dermatitis. Based on the severity of the side effects, the therapeutic dose is reduced by up to 50% of mRCC. A suitable route of administration would therefore be dosing based on the therapeutic monitoring of the levels (TDM) of sunitinib and its major metabolite of N-desethyl sunitinib (DES) in plasma. Effective concentrations range between 50-100 ng / ml and tandem mass spectrometry (MS) liquid chromatography (LC) is offered as an efficient and simple method for TDM. SUN and DES are subjected to reversible photochemical Z / E isomerization, which can make it difficult to determine the levels due to the equilibrium shift under conditions of light and dark. In addition, (E)-isomers are not available as analytical standards. Fast and simple LC MS with a resolution of individual isomers, using imatinib as an internal standard and the determination of total SUN and DES, was designed and tested on pilot sera of patients with mRCC. |
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