Investigation and structural elucidation of a new impurity in bulk drug of cilostazol by LC/MS/MS, FT-IR and NMR.

A new impurity was detected in bulk cilostazol (CIL) crude during routine analysis. The impurity (∼4%, the specification for unknown impurity in crude is not more than 0.20%) has a relative retention time of 1.46. Based on MS, NMR and IR spectral data, the impurity was identified as 6,6'-bis(4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy)-3,3',4,4'-tetrahydro-[7,7'-biquinoline]-2,2'(1H,1'H)-dione(CIL-dimer). The precursor of CIL-dimer is an oxidative product of starting material 6-Hydroxy-3,4-dyhydro-1H-quinolin-2-one(6-HQ), CIL-dimer was formed in the following reaction with 5-(3-Chloro-propyl)-1-cyclohexyl-1H-tetrazol(CHCBT).