Trace-Level Quantification and Identification of Mutagenic and Cohort-of-Concern N-nitroso-mirabegron Impurity (NDSRIs) using UFLC-ESI-MS/MS in Mirabegron

Currently, all the pharmaceutical industries and related industries have been dealing with issue from nitrosamine drug substance related impurities (NDSRIs) due to their potential health risks. Regulatory agencies provide guidelines for essential detail for generation pathways of their formation, severity, and permissible limits for human consumption. This research presents a trace-level quantification and identification, rapid, and high-sensitive LC-MS/MS technique for N-nitroso-mirabegron (NDSRIs) impurity in mirabegron with a LOQ of 0.8 µg/mL. The QSAR results are positive for N-nitroso-mirabegron, and the cohort of concern (CoC) suggests possible genotoxicity. Inert Sustain PFP (4.6mm x 150mm), 5µ HPLC column and mobile phase A contain 0.63 g/L of ammonium formate, methanol, and acetonitrile in a 4:3:3 (v/v/v) ratio while mobile phase B contain 0.2% formic acid in methanol. Positive ionization in Electron spray ionization (ESI) and multiple reaction monitoring (MRM) detection uses for identification and quantification. Linearity range of 0.8µg/mL to 12µg/mL with regression coefficient >0.990, precision (%RSD = 1.8, %RSD of Method precision = 3.01 and Intermediate Precision = 5.47). Accuracy within the range 84.55–91.64% within limit. While screening mirabegron samples for NDSRIs, the presence of N-nitroso-mirabegron was detected.