Department of Pharmaceutical Chemistry, Maulana Azad Education Trust's Y.B. Chavan College of Pharmacy, Aurangabad, India.
J Chromatogr Sci. 2020 Jul 24;58(7):661-671. doi: 10.1093/chromsci/bmaa034.
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.
氯卡色林（LOR）是一种选择性和有效的抗肥胖药物，靶向激活血清素 5HT2C 受体。本研究采用质量源于设计原理，开发并验证了一种新颖、特异、灵敏的专属性含量测定方法，用于定量测定 LOR 及其工艺相关杂质。通过应用实验设计，作者考察了参数对关键分离度对的多因素影响，并生成了代表稳健设计的设计空间。LOR 在所有条件下均稳定，仅在氧化应激条件下发现明显降解。在 Phenomenox Luna 苯基-己基柱（150×4.6mm×5μm）上实现了降解产物及其工艺相关杂质的色谱分离，流动相由 10mM 甲酸铵含 0.1%氨溶液组成；用三氟乙酸调节 pH 值至 2.8，溶剂 A 为甲醇/乙腈（5/95），采用梯度程序以 1.0mL/min 的流速洗脱，柱温保持在 25°C，在 220nm 处监测分析物。进样量为 5μL。所建立的反相高效液相色谱法经过验证，具有线性、准确、专属性、选择性、精密度和稳健性。杂质的结构通过直接质谱分析得到确认。
