Identification and characterization of new impurities in zopiclone tablets by LC-QTOF-MS

• The stability of zopiclone tablets were investigated according to the ICH guidelines. • Nine impurities in stability test samples were characterized by LC-QTOF-MS. • The origins and formation mechanisms of impurities were determined. • A new impurity confirmed as an adduct of hydrolysis product of zopiclone and lactose. • The results are useful for quality assurance and process control of zopiclone tablets. Zopiclone, a non-benzodiazepine hypnotic, is the first-line treatment for insomnia. The quality and stability of zopiclone tablets directly affects its efficacy and safety. However, the impurity investigation in zopiclone tablets remain incomplete. In this study, the accelerated and long-term stabilities of zopiclone tablets, as well as the stability characteristics under thermal and photolytic conditions were evaluated according to the ICH guidelines. In addition, a sensitive and specific LC-QTOF-MS method was developed for the separation and identification of all the impurities in zopiclone tablets and its stability test samples. Nine impurities were found in the test samples, five among them have not been reported before. Based on the accurate mass and elemental compositions of the parent and product ions obtained, the structures of all the detected impurities were identified. Combined with the formulation composition analysis and stability studies, the origins and the formation mechanisms of these impurities were elucidated. The obtained results are useful for the establishment of the optimum formulation, storage condition, manufacturing processes and quality control of zopiclone tablets.