Rapid microwave-assisted hydrolytic degradation of colchicine: In silico ADME/Tox profile, molecular docking, and development of innovative RP-Chromatographic methods

摘要

Colchicine, is a natural amide containing and-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, 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 performed using flash chromatography, structure was elucidated using H-1 NMR data. Moreover, results of human pharmacokinetic predictions conducted from in silico data showed that colchicine had higher blood brain barrier, plasma protein binding, and oral absorption than its deacylated derivative. The study was 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 degradate 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 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 degradate.