DEVELOPMENT AND VALIDATION OF AN LC-MS/MS METHOD FOR NITROSAMINE IMPURITY DETECTION IN TAMSULOSIN HYDROCHLORIDE

Objective: Regulatory oversight of pharmaceuticals containing nitrosamine contaminants has intensified in the past few years. Unites States Food and Drug Administration (USFDA), European Medicines Agency (EMA) and other regulatory agencies has been quite proactive in sending out warnings, instructions, and safety messages. This study presents a fast, accurate, and selective way to detect and quantify nitrosamine contaminants in Tamsulosin HCl. Methods: The purification of Tamsulosin using Di Methyl Formamide (DMF) requires monitoring to avoid nitrosamine formation. A 150 × 4.6 mm Symmetry® C18 column (5 µm, 40±1 °C) was used with a mobile phase involving water (98%), acetonitrile (2%) with 0.1% formic acid, where flow velocity was 0.8 ml/min and 10 µl** injection volume. After 1.20 min, the mobile phase composition gradually changed to 90% B (acetonitrile) and 10% A (water). Chromatographic separation took 10 min with a 5±0.5 °C auto-sampler temperature. Atmospheric Pressure Chemical Ionization (APCI) in positive ion mode, with clustering potentials of 36–50 V and collision energy of 9–30 eV, was used for quantification. Results: Following International Conference Harmonization (ICHQ2R1), showed regression value more than 0.997 and a signal-to-noise ratio of 3.7-4.5 ppm. Approach achieved Limit of Detection (LOD) values over 3.3-12.7 ppm and Limit of Quantification (LOQ) values over 9.9-36.9 ppm, with signal-to-noise ratios greater than 3.7% and greater than 12.9. All of the method recoveries fell between 80% and 120%. Conclusion: This Liquid Chromatography with Tandem Mass Spectroscopy (LC-MS/MS) technology detects and quantifies nitrosamine impurities in Tamsulosin quickly, sensitively and specifically, assuring regulatory compliance pursuant to USP General chapter<1469>. Impurities in Tamsulosin can be detected at a minimum level using the current technology, which allows for regular analysis.