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HIGHLY SENSITIVE MASS SPECTROMETRIC METHOD FOR DETERMINATION OF RETINOIC ACID USING METAL ORGANIC FRAMEWORKS

Název česky Vysoce citliva metoda pro stanovení kyseliny retinové pomocí hmotnostní spektrometrie (MALDI –TOF MS) s použitím Metal Organic Frameworks (MOF´s)
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HAJTMANOVÁ Kristína KUČERA Lukáš PEŇA MENDÉZ Eladia Maria JOSÉ ELIAS Conde Gonzáles VAŇHARA Petr HAMPL Aleš HAVEL Josef

Rok publikování 2016
Druh Další prezentace na konferencích
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
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Popis Retinoic acid (RA) is an active cellular retinoid metabolite and it is synthesized in cells from provitamin A. This metabolite has wide range of effects on vertebrate development and plays a crucial role during reproduction, proliferation, homeostasis, and physiopathology. It is frequently used to promote neural differentiation of pluripotent cells. All-trans RA is used in the differentiation therapy of acute promyelocytic leukemia. RA is thus biologically and clinically important molecule with a need of development of precise analytical determination allowing detection of very low amount of RA in complex biological samples1,2. Fig. 1 All-trans retinoic acid We employed here several mass spectrometric approaches, including either Matrix- or Surface- Assisted Laser Desorption Ionization Time Of Flight (MALDI- or SALDI- TOF), in order to reach highly sensitive determination of RA. First we explored possibilities of the use common MALDI-TOF matrices 2,5-dihydroxybenzoic acid (DHB)3, a-cyano-4-hydroxycinnamic acid (CHCA), and sinapinic acid (SA). The highest ionization of RA was observed using CHCA matrix and much lower detection limit was reached, (5 x) when compared with previously reported DHB3. Next, we used several metal organic frameworks (MOFs) such as HKUST-1, Basolite F300, and Cobalt(II) oxopivalat for SALDI-TOF MS. MOFs represent highly advanced porous materials which are known to absorb various molecules and/or nanoparticles4. Several experimental setups were outlined: (i) only pure MOFs were used for SALDI, to enhance RA desorption from the MOF crystals surface, or (ii) to test if pre-concentration of RA on MOFs is possible, or (iii) the combination of MOF (Basolite F300) with previously adsorbed gold nanoparticles, or (iv) the use of magnetic core-shell MOFs was examined, that showed the highest sensitivity in RA detection. The lowest detection limit (D.L.) was estimated to 10-13 mol. The use of MOFs as SALDI matrices for MS determination of RA is reported here for the first time. To validate our method, we determined RA in biologically very complex milieu of extracts of mouse embryonic fibroblasts. The results achieved open new possibilities of highly sensitive determination of retinoic acid and retinoids in highly complex and analytically difficult samples. In summary, new, highly sensitive method for RA pre-concentration and determination using MOFs was developed. Low D.L. enables determining the levels of RA in variety of biological or biomedical scenarios.

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