Identification and characterization of process related impurities in pramipexole dihydrochloride monohydrate

Pramipexole dihydrochloride monohydrate is used for treatment of idiopathic Parkinson’s disease. During routine monitoring of the drug samples by HPLC, two impurities of pramipexole were observed. The molecular weights of the impurities were determined by LC-MS. The structures were postulated to be (6S)-(-)-2-amino-6-ethylamino-4,5,6,7-tetrahydrobenzo thiazole (ethyl pramipexole) and (6S)-(-)-2,6-di-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole (dipropyl pramipexole). These were synthesized subsequently, and characterized by NMR and IR. Their presence was confirmed by spiking into pramipexole sample and carrying out HPLC analysis. To our knowledge, ethyl pramipexole and dipropyl pramipexole have not been reported as process impurities elsewhere.