Analytical aspects of sunitinib and its geometric isomerism towards therapeutic drug monitoring in clinical routine

Publication date: Available online 8 August 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Bianca Posocco, Mauro Buzzo, Luciana Giodini, Sara Crotti, Sara D’Aronco, Pietro Traldi, Marco Agostini, Elena Marangon, Giuseppe ToffoliAbstractSunitinib malate, an oral multi-targeted tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma, gastrointestinal stromal tumor, and well-differentiated pancreatic neuroendocrine tumors, has been identified as a potential candidate for therapeutic drug monitoring approach. Nevertheless, the development of an analytical assay suitable for clinical application for the quantification of the plasma concentration of sunitinib and its active metabolite, N-desethyl sunitinib, is limited by its Z/E isomerization when exposed to light. Several LC-MS/MS methods already published require protection from light during all sample handling procedures to avoid the formation of E-isomer, which makes them not suitable for clinical practice.In order to obtain a simple and fast procedure to reconvert the E-isomer, formed during sample collection and treatment without light protection, and, thus, to have only Z-isomer peak to quantify, we studied the Z/E photodegradation with special attention to the condition allowing the reverse reaction in plasma matrix.After 30 min of light exposure, the E-isomer maximum percentage of both the analytes was reached (44% of E-sunitinib and 20% of E-N-desethyl ...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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Conclusions: the early use of IVIG could contribute to an improvement and/or stabilization of visual symptoms in this patient group due to its rapid effect and lower profile of adverse effects when administered with chemotherapy. PMID: 31710513 [PubMed - as supplied by publisher]
Source: Ocular Immunology and Inflammation - Category: Allergy & Immunology Tags: Ocul Immunol Inflamm Source Type: research
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Source: The American Journal of Surgery - Category: Surgery Source Type: research
Publication date: Available online 11 November 2019Source: Academic RadiologyAuthor(s): Jing Ye, Qing Xu, Shou-An Wang, Jin Zheng, Wei-Qiang DouRationale and ObjectivesTo evaluate the diagnostic value of intravoxel incoherent motion and diffusion kurtosis imaging parameters for clear cell renal cell carcinoma (ccRCC) grading.Materials and MethodsA total of 60 patients with pathologically proven ccRCC who underwent intravoxel incoherent motion and diffusion kurtosis imaging were retrospectively evaluated. The standard apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fr...
Source: Academic Radiology - Category: Radiology Source Type: research
Publication date: Available online 11 November 2019Source: Pathology - Research and PracticeAuthor(s): Heejin Bang, Soomin Ahn, Eun Ji Kim, Seung Tae Kim, Ha Young Park, Jeeyun Lee, Kyoung-Mee KimABSTRACTRapamycin-insensitive companion of mTOR (RICTOR) is a key component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2), and promotes cellular proliferation and survival through the activation of downstream AGC kinase family members. The amplification of RICTOR has been proposed as a therapeutically relevant genomic alteration. However, other than next-generation sequencing, precise diagnostic methods to detect RICT...
Source: Pathology Research and Practice - Category: Pathology Source Type: research
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Source: Pathology Research and Practice - Category: Pathology Source Type: research
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We present the key trials and data for sunitinib that established it as a reference standard of care for first-line advanced RCC therapy and, along with other targeted agents, significantly altered the treatment landscape in RCC. Moreover, we discuss the research with sunitinib that has sought to refine its role via patient selection and prognostic markers, improve dosing and adverse event management, and identify predictive efficacy biomarkers, plus the extent to which this research has contributed to the overall understanding and management of RCC. We also explore the key learnings regarding study design and data interpr...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Review, Genitourinary Cancer Source Type: research
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