Tesis doctorado / doctoral thesis

Solid-phase-extraction of tamoxifen and its major metabolites from human-blood-plasma using electrospun polyacrylonitrile/metal-organic-frameworks nanocomposites for potential applications in breast cancer hormonal therapy monitoring.

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Abstract

Breast cancer is a major public health concern with a high level of mortality. Tamoxifen hormonal therapy has been shown to reduce the risk of recurrence and improve survival outcomes in certain types of breast cancer. Despite its effectiveness, not all breast cancer patients are eligible for or benefit from tamoxifen therapy. Moreover, tamoxifen is associated with potential side effects, such as blood clots and uterine cancer. Therefore, decisions regarding the use of tamoxifen should be based on a careful assessment of individual risk-benefit profiles. It has been found that Tamoxifen is a prodrug that produces Endoxifen and 4-hydroxitamoxifen, which are more pharmacologically active. Moreover, there is a relation between endoxifen levels in the blood and the effectiveness of Tamoxifen therapy. Typically, these metabolites are monitored using High Performance Liquid Chromatography coupled with tandem Mass Spectrometry (HPLC-Ms/Ms), which is expensive, requires specialized technical expertise, and might be less accessible for some healthcare facilities. In this research are designed and manufactured a series of solid-phase extractors (SPE) using electrospun nano-fibers containing several Metal-Organic-Frameworks (MOFs). The MOF's high porosity, tunable functionality, and structural diversity, along with the electrospun fibers high surface area and mechanical strength, are promising chromatographic tools. The nano-composed SPE were studied from the theoretical perspective as well as a comprehensive characterization to determine their selectivity, specificity, sensitivity, and stability towards Tamoxifen, Endoxifen, N-desmethyl tamoxifen, and 4-hydroxitamoxifen.

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https://orcid.org/0000-0003-2623-2080

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