Desenvolvimento de sorvente monolítico de poli(TMPTA-co-EDMA-co-MAA) impresso molecularmente para extração em ponteira descartável de nitrosaminas em formulações farmacêuticas

Abstract

Fast, environmentally friendly and portable sample preparation methods for chemical analysis have been widely sought after. One method that has received attention is disposable tip extraction (DPX), in which a particulate sorbent is dispersed inside a tip, retained by Teflon filters. However, two factors still limit further applications of DPX (i) low availability of sorbents, limiting its selectivity and (ii) the pressure required for suction and dispensing of liquids due to the resistance caused by the Teflon filters. The aim of this work is to make DPX fully portable and selective by preparing and functionalizing macroporous polymer monoliths inside disposable tips. Thus, in situ thermo-polymerization of trimethylolpropane triacrylate (TMPTA), methacrylic acid (MAA) and ethylene glycol dimethacrylate (EDMA) was carried out using 2,2-azobisisobutyronitrile as a radical initiator and polyethylene glycol (PEG) and isopropanol as porogens at 60 °C for 20 hours. The monolith was functionalized via molecular imprinting (MIP) of N-nitrosodimethylamine (NDMA). The preparation of the monolithic sorbent was optimized by evaluating the molar ratios of TMPTA:EDMA, monomer:porogenic solvent and MAA:NDMA, and porogenic solvents, monitoring the flow of liquids through the monoliths. The monoliths molded on the tip with 100 µL of the monomer mixture had the following optimum preparation conditions: isopropanol and PEG as porogenic solvents, TMPTA:EDMA:MAA:porogenic ratio (4%:14%:2%:80%). The poly(TMPTA-co-MAA-co-EDMA) monoliths molecularly imprinted with NDMA showed a globular solid structure with long interconnected channels, macroporosity > 60 % and a specific surface area of up to 81 m2 g-1, resulting in liquid flow rates of 1.24 mL min-1. The molecular printing of NDMA was optimized at a molar ratio of 1,28 mmols:1 mol of MAA:NDMA, with a imprinting factor of 3.75. The poly(TMPTA-co-MAA-co-EDMA) monoliths imprinted with NDMA were optimized for the DPX flow extraction of NDMA from aqueous samples of pharmaceutical formulations, establishing as optimum conditions 2.0 mL of sample in a single cycle and elution with 500 µL of acetonitrile in two cycles. The extracts obtained were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). The proposed DPX method resulted in a flow extraction of NDMA of 70%, with a concentration factor of 4x and a quantification limit of 1.71 ng mL-1. Thus, the DPX method with poly(TMPTA-co-MAA-coEDMA) imprinted with NDMA operates in flow extraction mode and can be considered simple, selective to NDMA, with good detectability, economical and totally portable, making it an alternative for determining the contaminant in pharmaceutical formulations.