Accurate identification and control of genotoxic impurities, also known as mutagenic impurities, during the development process of a drug substance are critical to product quality and patient safety. Periodic verification testing is an important requirement to demonstrate that the pharmaceutical product meets the acceptable limits and does not pose significant risk to human health.
This application note describes a sensitive and rapid UPLC method coupled with mass detection for the quantitative determination of two genotoxic impurities (GTI) of imatinib mesylate, an anti-neoplastic (anti-cancer) drug used in the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Two of its process impurities are classified as potential GTIs and must be monitored during the synthesis process.
The Xevo TQ-S micro method with MRM acquisition mode was developed for the ultra low-level detection of genotoxic impurities of imatinib mesylate API. Utilizing the RADAR function of the MassLynx Software allows acquisition of the full MS scan data simultaneously with the targeted MRM data in a single injection. This enables a quick and accurate assessment of the background matrix for potential presence of additional impurities in the sample or interference with the targeted analytes. The low-detection Xevo TQ-S micro method can be applied for monitoring the fate and purging levels of genotoxic impurities during the development process of the drug substance.
Controlled by a compliant-ready Empower 3 Software, the ACQUITY UPLC H-Class System coupled with an ACQUITY QDa Mass Detector is suitable for routine monitoring of genotoxic impurities in the late stage development of pharmaceutical products through QC environments.