Studying Microwave-Assisted Hydrolytic Degradation of Colchicine using RP-Chromatographic Methods: In Silico ADME/Tox Profile and Molecular Docking

Colchicine, is a natural amide containing anti-gout treatment with versatile applications. Microwave assisted hydrolytic degradation is a newly alternative method thought to be more promising than traditional procedures of heating. It is an ecofriendly method that has more reproducible results due to the control of parameters. From this point, carrying on hydrolytic degradation of colchicine was tested for the first time under acidic conditions with the aided of microwave. The drug was hydrolyzed with the formation of deacylated analogue. Isolation of the resulted degradate was carried out using flash chromatography, the isolated one was elucidated based on 1 H NMR data. Moreover, the results of human pharmacokinetic predictions conducted from in silico data showed that colchicine had higher blood brain barrier (BBB), plasma protein binding, and oral absorption than its deacylated derivative. The study was also extended to forecast the binding of colchicine and its degradate to the target protein. Furthermore, two stability indicating chromatographic methods were developed for quantification of the drug and its degradation product with high sensitivity. The first method was RP-TLC densitometric method that based on using a solvent mixture of water: methanol: diethylamine (70: 30: 15, by volume). The second one was RP-HPLC at which a mixture of water (containing 0.02% diethyl amine): methanol: acetonitrile (50: 20: 30, by volume) was the used mobile phase. Validation parameters were calculated according to ICH recommendations and all were within the acceptable limits. These methods were used for determination of colchicine in its available tablets. They are the first developed stability indicating methods for analysis of colchicine and its degradation product.