GC and HPLC-RID method development and validation for the determination of twelve related substances, including several novel compounds in tetrabenazine
Dong-shuo Meng , Guo-jing Li , Shen-guo Sun , Chun-xin Ma , Tian-quan Zhu , Yu Liu
{"title":"GC and HPLC-RID method development and validation for the determination of twelve related substances, including several novel compounds in tetrabenazine","authors":"Dong-shuo Meng , Guo-jing Li , Shen-guo Sun , Chun-xin Ma , Tian-quan Zhu , Yu Liu","doi":"10.1016/j.jpba.2025.116814","DOIUrl":null,"url":null,"abstract":"<div><div>A series of GC-FID and HPLC-RID methods were developed and rigorously validated for the detection of various aldehyde and ketone impurities, including 5-methyl-2-hexanone and 5-methyl-3-hexen-2-one, as well as quaternary ammonium salt impurity that lack UV absorption, during the synthesis of tetrabenazine. Six novel compounds, three have not been previously reported, were synthesized and their structures confirmed. This was achieved through a comprehensive investigation into impurity transmission chains and their clearance throughout the synthesis process. The limits for all detected impurities, which included a total of twelve related substances, were established at approximately 0.1 %. The LOD for the developed analytical methods ranged from 0.3 μg mL<sup>−1</sup> to 12.5 μg mL<sup>−1</sup>.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116814"},"PeriodicalIF":3.1000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmaceutical and biomedical analysis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0731708525001554","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
A series of GC-FID and HPLC-RID methods were developed and rigorously validated for the detection of various aldehyde and ketone impurities, including 5-methyl-2-hexanone and 5-methyl-3-hexen-2-one, as well as quaternary ammonium salt impurity that lack UV absorption, during the synthesis of tetrabenazine. Six novel compounds, three have not been previously reported, were synthesized and their structures confirmed. This was achieved through a comprehensive investigation into impurity transmission chains and their clearance throughout the synthesis process. The limits for all detected impurities, which included a total of twelve related substances, were established at approximately 0.1 %. The LOD for the developed analytical methods ranged from 0.3 μg mL−1 to 12.5 μg mL−1.
期刊介绍：
This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome.
Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
