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

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.

Liquid chromatographic separation and thermodynamic investigation of lorcaserin hydrochloride enantiomers on immobilized amylose-based chiral stationary phase.

A novel liquid chromatographic method was developed for enantiomeric separation of lorcaserin hydrochloride on Chiralpak IA column containing chiral stationary phase immobilized with amylose tris (3.5-dimethylphenylcarbamate) as chiral selector. Baseline separation with resolution greater than 4 was achieved using mobile phase containing mixture of n-hexane/ethanol/methanol/diethylamine (95:2.5:2.5:0.1, v/v/v/v) at a flow rate of 1.2 mL/min. The limit of detection and limit of quantification of the S-enantiomer were found to be 0.45 and 1.5 µg/mL, respectively; the developed method was validated as per ICH guideline. The influence of column oven temperatures studied in the range of 20°C to 50°C on separation was studied; from this, retention, separation, and resolution were investigated. The thermodynamic parameters ΔH°, ΔS°, and ΔG° were evaluated from van't Hoff plots,(Ink' versus 1/T) and used to explain the strength of interaction between enantiomers and immobilized amylose-based chiral stationary phase.