Validated LC-MS/MS method for ultra-trace determination of N-nitroso-desmethyl sumatriptan in sumatriptan succinate injection.
TL;DR
A rapid and highly sensitive LC-MS/MS method was developed and validated for the determination of the nitrosamine drug substance-related impurity N-nitroso-desmethyl sumatriptan (NNDS) in sumatriptan succinate injection, demonstrating excellent specificity, linearity, precision, accuracy, robustness, and solution stability.
Abstract
A rapid and highly sensitive LC-MS/MS method was developed and validated for the determination of the nitrosamine drug substance-related impurity N-nitroso-desmethyl sumatriptan (NNDS) in sumatriptan succinate injection. Separation was achieved on an Inertsil ODS-3 column using gradient elution with 0.1% formic acid in water and acetonitrile, followed by positive electrospray ionization in multiple reactions monitoring mode. The method was validated according to ICH Q2(R2) and USP <1225> guidelines, demonstrating excellent specificity, linearity (R² = 1.0000), precision, accuracy, robustness, and solution stability. The limits of detection and quantification were 0.05 ppm and 0.15 ppm, respectively, providing sensitivity well below the regulatory specification limit for NNDS. Analysis of commercial injection batches confirmed NNDS levels within acceptable limits. The validated method is suitable for routine quality control, stability assessment, and regulatory monitoring of nitrosamine impurities in pharmaceutical products.