Since the first commercial availability of gas chromatographs coupled with a combustion furnace and an isotope ratio mass spectrometry in 1990, compound-specific stable isotope analysis of organic molecules has been at the origin of scientific breakthroughs in a wide range of research fields. The presence of non-reacting atoms, however, can mask changes in molecular stable isotopic signatures; position-specific isotope analysis (PSIA) is the study of intramolecular isotopic variations. After a brief consideration of the potential and prospect of this new level in isotopic studies, in this study, we review few existing custom-built systems for on-line PSIA using continuous flow isotope ratio mass spectrometry instrumentation and how researchers have addressed issues related to this technique. Molecular fragmentation processes observed and optimised for various molecules are also discussed for on-line PSIA, as it would provide information on their application to new compounds
