Trace level quantification of N-Nitrosorasagiline in Rasagiline tablets by LC-TQ-MS/MS

Ann Pharm Fr. 2024 Mar 26:S0003-4509(24)00041-5. doi: 10.1016/j.pharma.2024.03.006. Online ahead of print.ABSTRACTParkinson's disease is a chronic, progressive neurological disease that currently affects about more than 10 million population worldwide. Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease. Rasagiline tablets have been recalled from market due to the presence of unacceptable levels of nitrosamine impurity. European medical agency has set up very stringent limit 100 ng/day of N-nitrosorasagiline (NSRG) in drug product based on its mutagenicity. The analytical methods need to be sufficiently sensitive in order to adequately detect and quantify trace levels of NSRG. A highly sensitive LC-MS/MS method for determination of NSRG in rasagiline tablet formulation was developed by effectively separating on zorbax eclipse XDB C18 column using 0.1% formic acid in mixture of water and acetonitrile (35:65 v/v) in an isocratic mode at 0.5 mL/min flow rate. The measurement of NSRG was performed using triple quadrupole mass detection accompanied by electrospray ionization in the multiple reaction monitoring mode. The validation of the method was comprehensive, demonstrating strong linearity across the concentration spectrum of 1 to 200 ng/mL for NSRG. The obtained correlation coefficient exceeded 0.998, signifying a robust relationship. Recoveries spanning from 80.0% to 120.0% for NSRG were deemed satisfact...
Source: Annales Pharmaceutiques Francaises - Category: Drugs & Pharmacology Authors: Source Type: research