Synthesis of molecularly imprinted polymers as selective solid phase extraction sorbents for anticancer drugs prior to chromatographic determination

Abstract

In recent years, the number of usage of chemotherapic drugs has considerably increased. It is necessary to develop analytical methods to analyse these compounds for quality control of formulations, quality control of diluted formulations before patient usage and understanding compatibility and stability. In this study, novel analytical methods were developed for mostly used anti cancer drugs, namely 5-fluorouracil (5- FU) and 5-azacytidine (5AC). Firstly, two analytical methodologies using capillary electrophoresis (CE) and liquid chromatography (LC) were developed for the determination of 5-FU and 5AC. The CE analysis was performed in a bare fused-silica capillary with 75 μm i.d. and total length of 50.0 cm with a buffer solution of 10.0 mM borate buffer, pH 11.5. The applied voltage was 20.0 kV. The LC analysis was performed with a YMC 30 column in reversed phase and a mobile phase of water–acetonitrile (90:10) at a flow rate of 0.8 mL/min. In both analyses, detection was by ultraviolet absorption. Also, molecularly imprinted polymers (MIPs) with different formulations (different functional monomers, porogens and monomer:crosslinker ratios) and morphologies (monolith and micro/nanosphericalbeads) were synthesized by using bulk and precipitation polymerization strategies. The adsorption capacity of imprinted polymers were compared to their corresponding non-imprinted polymer. MIP prepared by using bulk polymerization strategy with the formulation of 1:1:20 AA was chosen as selective solid phase extraction (SPE) sorbent due to its sorption capacity prior to determination of HPLC-DAD analysis. Selectivity of this imprinted polymer were examined by using 5-FU and 5AC molecules. To improve method, parameters were tested such as pH shaking time and amount of sorbent. So, optimization parameters of method were determined to be pH 5.0 of solution, 100.0 mg of sorbent, 10.0 mL 100.0 mg/L working solution, 60.0 min. sorption time.