Simultaneous $^{19}F$ NMR analysis of carboxylic acids in human plasma using selective $^{19}F$ labeling

Abstract

Carboxylic acids are crucial metabolites for understanding metabolic disorders and disease diagnosis. In this work, we developed selective $^{19}F$ labeling protocol for carboxylic acids in complex biofluids, employing pivaloyl chloride as an amide coupling reagent. By masking reactive functional groups such as thiols, amines, and alcohols, it enables the specific fluorine tagging of carboxylic acids, those selectively activated to the acid anhydrides. We examined the $^{19}F$ chemical shifts of 79 carboxylic acids and constructed the fingerprint region. Based on this newly developed method, we achieved simultaneous identification of carboxylic acid containing metabolites in human plasma and successfully quantified both small organic acids and fatty acids. This novel analytical method shows great potential for gaining valuable insights into the metabolic processes of living organisms.