2020 Volume 4 Issue 1 Pages 24-35
Gas chromatography (GC) is widely used in various fields. Among GC detectors, mass spectrometry detection (MS) provides highest selectivity and sensitivity, thus it is the most used detector especially in metabolomics studies. In GC-MS analysis, derivatization is mostly unavoidable for most of the analytes in order to increase volatility, thermal stability, and detectability of the analytes. Nevertheless, chemical derivatization has some limitations including uncertainty in quantitation, differences in derivatization kinetics, and the stability for variable analytes. Thus, the GC-MS analysis strongly requires standardizing protocols. One of the most used protocols for standardization is isotope dilution strategy. However, available isotope-internal standards are limited in number and expensive. A cost-effective and simpler alternative is isotope-coded derivatization (ICD), in which the standard or the control sample is labeled with a heavy isotope-coded moiety of the reagent and used as internal standards. On the other hand, the sample is labeled with the light form of the reagent. Then, both mixed and analyzed by GC-MS (/MS) permitting the absolute quantification of analytes and identification of unknown ones. Due to the high importance of ICD, there are many reviews summarized its use in LC-MS analysis. However, there is no single review dedicated to summarizing its use in GC-MS. Until now, few types of reagents were designed for ICD for GC-MS applications. These reagents can be classified into silylation, chloroformates esterification, transmethylation, and aminooxyethyl propionates oximation ICD reagents. In this review, we will discuss every class of them and their reported applications with special emphasis on metabolomics.