Charge-Transfer Reaction of Cediranib with 2,3-Dichloro-3,5-dicyano-1,4-benzoquinone: Spectrophotometric Investigation and Use in Development of Microwell Assay for Cediranib

摘要

Purpose: To investigate the charge-transfer (CT) reaction between cediranib (CRB) and 2, 3 - dichloro- 5, 6- dicyano -1, 4 - benzoquinone (DDQ) and employment of the reaction as a basis for the development of a novel 96 - microwell spectrophotometric assay for CRB. Method: The reaction of CRB and DDQ was investigated in different solvents of varying dielectric constant and polarity index The reaction resulted in the formation of a red-colored product. Spectrophotometric investigations confirmed that the reaction proceeded through to the formation of a (CT) complex. Results: The molar absorptivity of the CT complex was linearly correlated with the dielectric constant and polarity index of the solvent; the correlation coefficients were 0.801 and 0.858, respectively. The association constant of the complex was 0.5 × 103 L mol?1 in 2-propanol. The reaction conditions were optimized for the development of the microwell assay for CRB. The assay limits of detection and quantitation were 6.8 and 20.6 μg/well, respectively. The assay was validated as per the guidelines of the International Conference on Harmonization (ICH) and successfully applied to the analysis of CRB in its bulk and dosage forms with good accuracy and precision. Conclusion: The developed assay has high throughput and consumed minimum volume of organic solvent; thus, it reduces the exposure of the analysts to the toxic effects of organic solvents, and should significantly lower the analysis cost.