Elucidation of several neglected reactions in the GC-MS identification of sialic acids as heptafluorobutyrates calls for an urgent reassessment of previous claims

The current analytical protocol used for the GC-MS determination of free
or 1,7-lactonized natural sialic acids (Sias), as heptafluorobutyrates,
overlooks several transformations. Using authentic reference standards
and by combining GC-MS and NMR analyses, flaws in the analytical
protocol were pinpointed and elucidated, thus establishing the scope and
limitations of the method. It was demonstrated that (a) Sias
1,7-lactones, even if present in biological samples, decompose under the
acidic hydrolysis conditions used for their release; (b) Sias
1,7-lactones are unpredicted artifacts, accidentally generated from
their parent acids; (c) the N-acetyl group is quantitatively exchanged
with that of the derivatizing perfluorinated anhydride; (d) the partial
or complete failure of the Sias esterification-step with diazomethane
leads to the incorrect quantification and structure attribution of all
free Sias. While these findings prompt an urgent correction and
improvement of the current analytical protocol, they could be
instrumental for a critical revision of many incorrect claims reported
in the literature.