使用UPLC-LTQ-Orbitrap-MS和HPLC-CAD来识别cycloastragenol中的杂质,这是COPD的临床前候选者
Feng Zhu1, Xiao Zhang1,2, Bing-Yuan Du1
1State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi 273400, China.
Molecules (Basel, Switzerland)
|September 9, 2023
概括
循环氨醇 (CAG) 是慢性阻塞性肺病 (COPD) 的潜在治疗方法,在大规模合成. 它的杂质被确定,一些新的化合物显示出抗炎作用,有助于药物安全和质量控制.
科学领域:
- 药理学和天然产品化学化学
- 药用化学 医学化学
- 药物开发 药物开发
背景情况:
- 慢性阻塞性肺病 (COPD) 是全球主要的死亡原因之一.
- 来自阿斯特拉加利根的循环氨醇 (CAG) 是COPD治疗的有希望的临床前候选者.
- 高效的大规模生产和全面的杂质分析对于药物开发至关重要.
研究的目的:
- 建立一个高效的大规模合成环氨醇 (CAG).
- 为了识别和描述CAG活性药物成分 (API) 中存在的杂质.
- 评估新杂质的抗炎潜力,并提出降解途径.
主要方法:
- 通过史密斯降解从阿斯特拉加洛西德IV (AS-IV) 来进行CAG的大规模合成.
- 使用HPLC-CAD和UPLC-LTQ-Orbitrap-MS进行杂质分析,因为紫外线吸收较弱.
- 使用柱状染色学,PTLC和光谱分析进行杂质的隔离和结构阐明.
主要成果:
- 在2.5公斤尺度上有效生产CAG.
- 从CAG API中确定了15种杂质,其中6种已被完全阐明,9种已被假定确定.
- 两种新型的10,19-secocycloartane三类化合物 (化合物9和14) 显示出抗炎活性.
结论:
- 该研究提供了一种可扩展的CAG生产方法和全面的杂质配置文件.
- 生物活性杂质的识别有助于CAG API的质量控制和临床安全评估.
- 拟议的降解途径为管理具有较差紫外线吸收特性的化合物提供了指导.
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