Current trends in isotope‐coded derivatization liquid chromatographic‐mass spectrometric analyses with special emphasis on their biomedical application

Abstract Currently, LC–MS has various applications in different areas such as metabolomics, pharmacokinetics, and pathological studies. Yet, matrix effects resulting from co‐existing constituents remain a major problem for LC–MS [or LC–tandem mass spectrometry (LC–MS/MS)]. Moreover, technical problems and instrumental drifts may lead to ion abundance variance. Thus, an internal standard (IS) is required to guarantee the accuracy and precision of the method. Because of their limited number, isotope‐coded derivatization (ICD) has been recently introduced to overcome this problem. For ICD, a stable heavy isotope‐coded moiety is used for labeling the standard or the control sample and the formed products can act as ISs. A light form of the reagent is used for labeling the sample. Then, both are mixed and analyzed by LC–MS(/MS). This strategy permits the identification of different unknown analytes including potential metabolites and disease biomarkers. All these attributes lead to persistent growth in the applications of ICD LC–MS(/MS) in various biomedical branches. In this article we review the ICD methods published in the last eight years for biomedical applications as well as briefly summarize other applications for environmental and food analyses as some of their used ICD reagents were further applied for analyzing biological specimens or have the potential for that.