A Validated Stability-Indicating Liquid Chromatographic Method for the Determination of Lorcaserin and Related Impurities in DRUG Substance Supported by Quality by Design

Abstract

Abstract Lorcaserin (LOR) is selective and potent antiobesity drug that targets the activation of the serotonin 5HT2C receptor. Here a novel, specific, sensitive stability indicating method was developed and validated for the quantitative determination of LOR and its process-related impurities using quality by design principles. By applying experimental design, the authors examine the multifactorial effect of parameters on the critical resolution pair and generated design space representing the robust design. LOR was subjected to stress condition and found stable at all condition, only found significant degradation at oxidative stress condition. The chromatographic separation of degradation product and its process-related impurities were achieved on a Phenomenox Luna phenyl-hexyl column (150 × 4.6 mm × 5 μm), with mobile phase consisting of 10 mM ammonium formate containing 0.1% ammonia solution; pH adjusted to 2.8 with trifluoroacetic acid as solvent A and methanol/acetonitrile (5/95) as solvent B delivered with gradient program at a flow rate of 1.0 mL/min, column temperature was maintained at 25°C and analytes were monitored at 220 nm. The injection volume was 5 μL. The developed RP-LC method was validated and found linear, accurate, specific, selective, precise and robust. The structure of impurities was confirmed by direct mass analysis.