{"title":"粉防己碱光化学降解的杂质谱及机理研究","authors":"Jinmei Tan, Feng Wang, Ruihan Zheng, Weiran Yang, Jinlong Chen","doi":"10.1002/rcm.10102","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Rationale</h3>\n \n <p>Tetrandrine is a bisbenzylisoquinoline alkaloid with diverse pharmacological activities and faces critical pharmaceutical challenges due to its inherent photolability under environmental stressors. Despite its therapeutic potential, systematic investigations into its photodegradation mechanisms and impurity profiling remain conspicuously absent, posing risks to drug quality control and regulatory compliance.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Structural elucidation of degradation products (DPs) was achieved through advanced analytical techniques, including high-resolution mass spectrometry (HRMS), 1D/2D nuclear magnetic resonance (NMR) spectroscopy, and comparative fragmentation analysis. Key degradation drivers—including light intensity, atmospheric composition, aqueous content, and pH extremes—were quantitatively assessed through designed single-variable experiments.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Seven photodegradants (DP-1 to DP-7) were structurally characterized, including two quaternary ammonium enantiomers (DP-2 and DP-3) from N-oxidation, a benzophenone derivative (DP-4) via benzylic C–H oxidation, and macrocyclic cleavage products (DP-1 and DP-7) through oxidative C–C bond scission. Degradation exhibited irradiance threshold behavior (> 10 mW cm<sup>−2</sup> for 80% conversion) and oxygen dependency (<i>R</i><sup>2</sup> = 0.98). Alkaline conditions (0.1 M NaOH) induced complete degradation within 0.5 h through ·OH-mediated radical chain reactions, while aqueous media (40% H<sub>2</sub>O) accelerated hydrolysis.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>This study provides the first mechanistic atlas of tetrandrine's photodegradation, identifying three dominant pathways: oxidative skeletal modification, oxidative ring-opening, and radical-mediated C–N cleavage. This study establishes a robust framework for the impurity analysis of natural product-derived drugs and provides actionable guidelines for stabilizing tetrandrine during manufacturing and storage.</p>\n </section>\n </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"39 20","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impurity Profiling and Mechanistic Investigation of the Photochemical Degradation of Tetrandrine\",\"authors\":\"Jinmei Tan, Feng Wang, Ruihan Zheng, Weiran Yang, Jinlong Chen\",\"doi\":\"10.1002/rcm.10102\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Rationale</h3>\\n \\n <p>Tetrandrine is a bisbenzylisoquinoline alkaloid with diverse pharmacological activities and faces critical pharmaceutical challenges due to its inherent photolability under environmental stressors. Despite its therapeutic potential, systematic investigations into its photodegradation mechanisms and impurity profiling remain conspicuously absent, posing risks to drug quality control and regulatory compliance.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Structural elucidation of degradation products (DPs) was achieved through advanced analytical techniques, including high-resolution mass spectrometry (HRMS), 1D/2D nuclear magnetic resonance (NMR) spectroscopy, and comparative fragmentation analysis. Key degradation drivers—including light intensity, atmospheric composition, aqueous content, and pH extremes—were quantitatively assessed through designed single-variable experiments.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Seven photodegradants (DP-1 to DP-7) were structurally characterized, including two quaternary ammonium enantiomers (DP-2 and DP-3) from N-oxidation, a benzophenone derivative (DP-4) via benzylic C–H oxidation, and macrocyclic cleavage products (DP-1 and DP-7) through oxidative C–C bond scission. Degradation exhibited irradiance threshold behavior (> 10 mW cm<sup>−2</sup> for 80% conversion) and oxygen dependency (<i>R</i><sup>2</sup> = 0.98). Alkaline conditions (0.1 M NaOH) induced complete degradation within 0.5 h through ·OH-mediated radical chain reactions, while aqueous media (40% H<sub>2</sub>O) accelerated hydrolysis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>This study provides the first mechanistic atlas of tetrandrine's photodegradation, identifying three dominant pathways: oxidative skeletal modification, oxidative ring-opening, and radical-mediated C–N cleavage. This study establishes a robust framework for the impurity analysis of natural product-derived drugs and provides actionable guidelines for stabilizing tetrandrine during manufacturing and storage.</p>\\n </section>\\n </div>\",\"PeriodicalId\":225,\"journal\":{\"name\":\"Rapid Communications in Mass Spectrometry\",\"volume\":\"39 20\",\"pages\":\"\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Rapid Communications in Mass Spectrometry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/rcm.10102\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Rapid Communications in Mass Spectrometry","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/rcm.10102","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Impurity Profiling and Mechanistic Investigation of the Photochemical Degradation of Tetrandrine
Rationale
Tetrandrine is a bisbenzylisoquinoline alkaloid with diverse pharmacological activities and faces critical pharmaceutical challenges due to its inherent photolability under environmental stressors. Despite its therapeutic potential, systematic investigations into its photodegradation mechanisms and impurity profiling remain conspicuously absent, posing risks to drug quality control and regulatory compliance.
Methods
Structural elucidation of degradation products (DPs) was achieved through advanced analytical techniques, including high-resolution mass spectrometry (HRMS), 1D/2D nuclear magnetic resonance (NMR) spectroscopy, and comparative fragmentation analysis. Key degradation drivers—including light intensity, atmospheric composition, aqueous content, and pH extremes—were quantitatively assessed through designed single-variable experiments.
Results
Seven photodegradants (DP-1 to DP-7) were structurally characterized, including two quaternary ammonium enantiomers (DP-2 and DP-3) from N-oxidation, a benzophenone derivative (DP-4) via benzylic C–H oxidation, and macrocyclic cleavage products (DP-1 and DP-7) through oxidative C–C bond scission. Degradation exhibited irradiance threshold behavior (> 10 mW cm−2 for 80% conversion) and oxygen dependency (R2 = 0.98). Alkaline conditions (0.1 M NaOH) induced complete degradation within 0.5 h through ·OH-mediated radical chain reactions, while aqueous media (40% H2O) accelerated hydrolysis.
Conclusions
This study provides the first mechanistic atlas of tetrandrine's photodegradation, identifying three dominant pathways: oxidative skeletal modification, oxidative ring-opening, and radical-mediated C–N cleavage. This study establishes a robust framework for the impurity analysis of natural product-derived drugs and provides actionable guidelines for stabilizing tetrandrine during manufacturing and storage.
期刊介绍：
Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
