Abstract

Lorcaserin (LOR) is selective and potent antiobesity drug that targets the activation of the serotonin 5HT_2C 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.

中文翻译：

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一种有效的稳定度指示液相色谱法，以质量为设计依据，用于测定DRUG物质中的酪蛋白和相关杂质。

摘要

Lorcaserin（LOR）是选择性和有效的抗肥胖药，其靶向血清素5HT _2C的激活受体。在此，开发了一种新颖，特异性，灵敏的稳定性指示方法，并通过设计原理验证了该方法用于使用质量定量测定LOR及其过程相关杂质的能力。通过应用实验设计，作者检查了参数对临界分辨率对的多因素影响，并生成了代表稳健设计的设计空间。LOR处于胁迫条件下，在所有条件下均稳定，仅在氧化应激条件下发现显着降解。在Phenomenox Luna苯基己基色谱柱（150×4.6 mm×5μm）上实现了降解产物及其过程相关杂质的色谱分离，流动相由含0.1％氨溶液的10 mM甲酸铵组成。pH调整至2。在图8中，以三氟乙酸作为溶剂A和甲醇/乙腈（5/95）作为溶剂B，以1.0mL / min的流速通过梯度程序进行输送，将柱温保持在25℃，并且在220nm下监测分析物。进样量为5μL。验证了开发的RP-LC方法并发现其线性，准确，特异，选择性，精确和鲁棒。通过直接质量分析确认了杂质的结构。