Nowadays, drug pollution; a form of water pollution caused by some pharmaceuticals and their metabolites resulting from consumers, industry and hospitals was reported. Colchicine (CLN) is considered one of the pharmaceutical wastewater contaminants which are not eliminated completely in municipal sewage treatment plants and are discharged into receiving water. Due to the higher toxicity of CLN, a novel heterogeneous Fenton's-like catalysis was established for complete degradation of CLN. So, a highly sensitive and specific liquid chromatographic method with quadrupole mass spectrometry (LC/Q-MS) was developed and validated for estimation of CLN in its pure form and in the presence of its degradation product. Herein, GraceSmart RP C18 column was utilized for separation of the cited drug (Retention time tR= 5.578 min) using methanol: water (55: 45, v/v) at 1.0 mL/min. Detection was performed by Agilent 6120 Quadrupole MS detector in a positive ionization mode. Thereafter and for the first time, degradation of CLN by heterogeneous Fenton's-like catalysis using modified polyacrylonitrile (PAN) as a catalyst with H2O2 in aqueous acidic medium was performed. This process was firstly optimized by HPLC/UV detection at 248 nm using the aforementioned chromatographic conditions. As a result, CLN degraded completely within 30 min. The only observed degradation product was the biologically active, potent and less toxic antitumor metabolite of CLN (3-demethyl CLN) which was collected, extracted, and analyzed by Fourier Transfer-Infrared Spectroscopy (FTIR) and 13Carbon-Nuclear Magnetic Resonance (13C-NMR). Finally, this method is eco-friendly and complies with the requirements of the green chemistry. It is suitable for complete removal of CLN and/or its metabolite contaminants from wastewater samples and estimation of the target drug without any interference from its degradation products. However, further study is required to expand the method applicability to the pharmaceutical wastewater treatment as well the production of 3-demethyl CLN on a large scale.