Application of HR CS GF-MAS for Determining the Intracellular Concentration of Fluorinated Drugs and Drug Candidates in Cancer Cells, Using Calcium Monofluoride (CaF) as the Target Molecule
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Fluorinated drugs and drug candidates are showing signs of becoming a cornerstone in the fight against cancer, a threat to the well-being of humanity. An HR CS GF-MAS method has been developed for quantifying their intracellular concentration in cancer cells, a prerequisite for efficacy and effectiveness. The study determined the intracellular concentration of the fluorinated drug 5 Fluoro uracil (5FU) and a drug candidate, [chlorido (Fe (III)4Fluoro Salophen)], an iron complex. The method presented here is very sensitive with a lower limit of quantitation of 3µg/L equivalent to 3ng/ml, accurate, with an accuracy range of 99.8-102.9%; it is fast, less than two minutes per sample, linear in the range of 12.5-600µg/l (R2=1), precision was demonstrated by the method, the highest coefficient of variance for inter and intra-day precision test was 5.1. A novel sample preparation approach using citric acid and tetramethyl ammonium hydroxide effectively extracted fluorides with high accuracy and precision. These reagents equally stabilized fluorides and prevented their loss in the form of hydrogen fluoride. These attributes enable the method to generate accurate and reliable data that informs the drug development process. The tested ability of the validated HR CS GF-MAS method to determine the intracellular concentration of both organofluorinated drugs and fluorinated metal complexes makes it a reliable tool for developing and testing fluorinated medications in general. Drug researchers may also use this method to explore the mechanism of fluorinated drug uptake in cells and analyse fluorinated drugs in other matrices.
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