通过 LC-MS/MS、高分辨质谱和 1D、2D NMR 对苏沃雷生原料药的 5 种氧化降解杂质和 1 种工艺杂质进行特征分析：用 HPLC 和 UPLC 对苏沃雷生原料药和工艺杂质进行验证。
Characterization of Five Oxidative Degradation Impurities and One Process Impurity of Suvorexant Drug Substance by LC-MS/MS, HR-MS and 1D, 2D NMR: Validation of Suvorexant Drug Substance and Process Impurities by HPLC and UPLC.
机构信息
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd, Miyapur, Hyderabad, Telangana 500049, India.
Department of Inorganic & Analytical Chemistry, Andhra University, Visakhapatnam, Andhra Pradesh 530003, India.
出版信息
J Chromatogr Sci. 2020 Apr 25;58(5):433-444. doi: 10.1093/chromsci/bmaa003.
During the oxidative (10% H2O2) degradation of suvorexant drug substance, around 1.0% of one impurity and less than 1.0% four impurities were found by a new high-performance liquid chromatography (HPLC) assay and related substance method. The mass numbers of 1.0% impurity was 469 [M + H]+, remaining four impurities were 172 [M + H]+, 467 [M + H]+, 483 [M + H]+ and 485 [M + H]+. The 469 [M + H]+, 485[M + H] and 172 [M + H]+ impurities were characterized by using the LC-MS/MS, HR-MS and 1D, 2D NMR spectroscopic data. The 172 [M + H]+ impurity was prepared synthetically and co-injected in HPLC. The retention time of synthesized 172 [M + H]+ impurity was matching with the unknown degradation impurity in HPLC. The developed mass compatible HPLC and ultra performance liquid chromatography methods were validated for drug substance and process impurities by following ICH Q2 (R1) guidelines.
在舒沃雷生药物的氧化（10% H2O2）降解过程中，通过一种新的高效液相色谱（HPLC）分析方法和有关物质方法，发现约有 1.0%的一种杂质和小于 1.0%的四种杂质。1.0%杂质的质荷比为 469 [M+H]+，其余四种杂质的质荷比分别为 172 [M+H]+、467 [M+H]+、483 [M+H]+和 485 [M+H]+。采用 LC-MS/MS、HR-MS 和 1D、2D NMR 光谱数据对 469 [M+H]+、485[M+H]和 172 [M+H]+杂质进行了表征。通过合成的方法制备了 172 [M+H]+杂质，并在 HPLC 中进行了共注射。合成的 172 [M+H]+杂质的保留时间与 HPLC 中未知降解杂质的保留时间相匹配。按照 ICH Q2（R1）指南，开发了与质量兼容的 HPLC 和超高效液相色谱方法，用于药物和工艺杂质的验证。
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