Background: Linifanib (LFB) is a multi-targeted receptor tyrosine kinase inhibitor used in
the treatment of hepatocellular carcinoma and other types of cancer. The charge-transfer (CT)
interaction of LFB is important in studying its receptor binding mechanisms and useful in the
development of a reliable CT-based spectrophotometric assay for LFB in its pharmaceutical
formulation to assure its therapeutic benefits.
Purpose: The aim of this study was to investigate the CT reaction of LFB with 2,3-dichloro-
3,5-dicyano-1,4-benzoquinone (DDQ) and its application in the development of a novel 96-
microwell spectrophotometric assay for LFB.
Methods: The reaction was investigated, its conditions were optimized, the physicochemical
and constants of the CT complex and stoichiometric ratio of the complex were determined.
The solid-state LFB-DDQ complex was synthesized and its structure was analyzed by
UV-visible, FT-IR, and 1H-NMR spectroscopic techniques, and also by the computational
molecular modeling. The reaction was employed in the development of a novel 96-microwell
spectrophotometric assay for LFB.
Results: The reaction resulted in the formation of a red-colored product, and the spectrophotometric
investigations confirmed that the reaction had a CT nature. The molar absorptivity
of the complex was linearly correlated with the dielectric constant and polarity index of
the solvent; the correlation coefficients were 0.9526 and 0.9459, respectively. The stoichiometric
ratio of LFB:DDQ was 1:2. The spectroscopic and computational data confirmed the
sites of interaction on the LFB molecule, and accordingly, the reaction mechanism was
postulated. The reaction was utilized in the development of the first 96-microwell spectrophotometric
assay for LFB. The assay limits of detection and quantitation were 1.31 and 3.96
μg/well, respectively. The assay was successfully applied to the analysis of LFB in its bulk
and tablets with high accuracy and precision.
Conclusion: The assay is simple, rapid, accurate, eco-friendly as it consumes low volumes
of organic solvent, and has high analysis throughput.
Keywords: linifanib, 2,3-dichloro-3,5-dicyano-1,4-benzoquinone, charge-transfer reaction,
spectroscopic techniques, 96-microwell spectrophotometric assay, high-throughput
pharmaceutical analysis
تاريخ البحث
مجلة البحث
Drug Design, Development and Therapy
الناشر
Dovepress
عدد البحث
15
موقع البحث
http://doi.org/10.2147/DDDT.S296502
سنة البحث
2021
المشارك في البحث
صفحات البحث
1167–1180
ملخص البحث