化学试剂2026，Vol.48Issue(9)：77-83,7.DOI:10.13822/j.cnki.hxsj.2026.0157
质谱及其联用技术在稳定同位素标记化合物的同位素纯度分析中的应用进展
Recent Advances of Mass Spectrometry and Its Hyphenated Techniques in Isotopic Purity Analysis of Stable Isotope-Labeled Compounds
摘要
Abstract
Isotopic purity of stable isotope-labeled compounds constitutes a fundamental and indispensable metric critically governing the reliability of investigative endeavors involving stable isotope-labeled compounds and the overarching accuracy of resultant experimental outcomes.Consequently,the rigorous and precise assessment of this pivotal parameter remained absolutely essential for ensuring the ultimate validity and robustness of research conclusions derived from such sophisticated studies.Given its demonstrably profound impact on research quality involving stable isotope-labeled compounds,the innovations and advances in analytical methodologies for isotopic purity assessment held considerable significance for continued progress across chemistry,biology,and translational medicine.This review systematically synthesized recent advances in mass spectrometry(MS)techniques for isotopic purity analysis of stable isotope-labeled compounds,providing a comprehensive and exhaustive overview of contemporary developments and practical applications.Specifically,gas chromatography-MS(GC-MS)proved optimal for volatile small organic molecules and derivatives amenable to vaporization,offering high chromatographic resolution for complex mixtures.In contrast,liquid chromatography-MS(LC-MS)demonstrated exceptional efficacy in characterizing polar organic compounds and biomolecules,benefiting from its versatility in handling non-volatile analytes.Furthermore,direct infusion utilizing ultra-high-resolution MS(e.g.,Orbitrap)enabled rapid,chromatography-free screening of pure stable isotope-labeled compounds via direct sample introduction,substantially reducing analysis time while streamlining analytical workflows.Our recent study innovatively developed an electrospray ionization high-resolution mass spectrometry(ESI-HRMS)-based workflow,integrated with a custom Python-driven computational program,to systematically address the challenges in isotopic purity analysis of both mono-isotope-labeled and mixed-isotope-labeled compounds.This method offered distinct advantages,including minimal sample consumption and rapid analysis speed,providing a reliable tool for the quality control of isotope-labeled compounds used across relevant scientific fields.When coupled with our custom-developed Python computational program,it significantly enhanced the efficiency of isotopic purity analysis.Moreover,isotope ratio MS(IRMS)furnished high-precision benchmark data owing to its exceptional accuracy,serving as an authoritative reference standard across diverse sample matrices.To address persistent challenges—notably discriminating isobaric interferences and implementing natural isotopic abundance subtraction—this review rigorously delineated key terminologies,including isobaric ions,isotopologs,and isobaric isotopologs.It offered precise definitions to promote methodological consistency while strictly distinguishing isotopic purity from the oft-conflated parameters of isotopic abundance and enrichment.Furthermore,we proposed the introduction of the"representative isotopolog ion"concept to refine computational models,thereby enhancing calculation robustness.This approach elucidated the necessity of prioritizing isotopic purity as the principal analytical metric to circumvent confounding signals from natural isotopic abundance at non-labeled sites,thereby providing a robust and enduring framework for the high-precision quantification of isotope-labeled compounds.关键词
同位素纯度/天然同位素丰度/同位素异构体/气相色谱-质谱法/液相色谱-质谱法/超高分辨率质谱法Key words
isotopic purity/natural isotopic abundance/isotopolog/gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry/ultra-high-resolution mass spectrometry分类
化学化工引用本文复制引用
梁辰龙,刘清钦,周博文,凌琳,王昊阳..质谱及其联用技术在稳定同位素标记化合物的同位素纯度分析中的应用进展[J].化学试剂,2026,48(9):77-83,7.基金项目
国家自然科学基金面上项目(21772227) （21772227）
中国科学院上海有机化学研究所自主部署项目(E22ZZ61) （E22ZZ61）
中国科学院战略性先导科技专项资助项目(XDB0590000). （XDB0590000）
