Identification and synthesis of potential process-related impurities of trametinib: an anti-cancer drug

Trametinib is used to treat patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. Two process impurities, namely 5-(2-fluoro-4-iodo phenylamino)-1-(3-aminophenyl)-3-cyclopropyl-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7 (1 H ,3 H ,6 H )-trione hydrochloride (2) and 4-((3-acetamidophenyl)amino)- N -cyclopropyl-2-((2-fluoro-4-iodophenyl)amino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide (3), are observed during the laboratory optimization of trametinib. These impurities have a definite impact on the quality of the drug product. In this context, the identification, synthesis, origin and the control of these potential impurities are described. This study will be helpful to the generic pharmaceutical industry for obtaining chemically pure trametinib.