Abstract
The tyrosine kinase inhibitors (TKIs) are chemotherapeutic drugs used for the targeted therapy of various types of cancer. This work discusses the experimental and computational evaluation of chloranilic acid (CLA) as a universal chromogenic reagent for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for TKIs. The reaction resulted in an instantaneous formation of intensely purple colored products with TKIs. Spectrophotometric results confirmed that the reactions proceeded via the formation of charge-transfer complexes (CTCs). The physical parameters were determined for the CTCs of all TKIs. Computational calculations and molecular modelling for the CTCs were conducted, and the site(s) of interaction on each TKI molecule were determined. Under the optimized conditions, Beer’s law correlating the absorbances of the CTCs with the concentrations of TKIs were obeyed in the range of 10–500 µg/well with good correlation coefficients (0.9993–0.9998). The proposed MW-SPA fully validated and successfully applied for the determination of all TKIs in their bulk forms and pharmaceutical formulations (tablets). The proposed MW-SPA is the first assay that can analyze all the TKIs on a single assay system without modifications in the detection wavelength. The advantages of the proposed MW-SPA are simple, economic and, more importantly, have high throughput.
Highlights
Cancer is the world’s second major cause of death among males and females
Since traditional CT-based spectrophotometric methods have a restricted throughput and utilize large volumes of organic solvents that are costly and, more crucially, cause toxicity to analysts [45,46,47,48], this study was dedicated to developing a spectrophotometric assay for tyrosine kinase inhibitors (TKIs) that is free from these demerits
Accomplishing this goal was achieved by performing a CT reaction between TKIs and chloranilic acid (CLA) in 96-microwell assay plates and recording the color intensity by a microplate absorbance reader
Summary
Cancer is the world’s second major cause of death among males and females. This reflects ~9.6 million deaths in 2018 (~13% of all deaths). The majority of health care systems in developed countries are little prepared to deal with this challenge, and many cancer patients globally will not have the privilege of early treatment. In these countries, nearly two-thirds of cancer patients die [6]. There is evidence that shows that in countries where national health services are well-developed, strategies such as early detection, treatment and survivorship care are improving the survival rates of many types of cancers [1,6]
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