Pentafluorobenzyl bromide – A versatile derivatization agent in chromatography and mass spectrometry: II. Analysis of organic acids and bases, and comparison with other perfluorinated reagents

Analytical derivatization is an important for the vast majority of substances an indispensable sample preparation step for their quantitative GC–MS and GC–MS/MS analysis in biological samples. Pentafluorobenzyl bromide (PFB-Br), pentafluorobenzoyl chloride (PFB-COCl), pentafluorobenzyl hydroxylamine (PFB-NHNH₂), pentafluorophenyl hydrazine (PFPh-ONH₂), pentafluoropropionic anhydride (PFPA), and heptafluorobutyric anhydride (HFBA) are versatile derivatization reagents in analytical chemistry. In the present work, the utility of the above mentioned derivatization reagents for the GC–MS analysis of carboxylic, aldehydic, hydroxylic and amine groups containing analytes including amino acids is reviewed and discussed. Derivatization requires different conditions for solvents, reaction temperature and time, and possibly for catalysts. The perfluorinated derivatives are electrically neutral and best soluble in water-immiscible organic solvents such as toluene. Under negative-ion chemical ionization (NICI) conditions, the perfluorinated derivatives readily and abundantly ionize that allows for sensitive analysis. In addition, the perfluorinated analyte derivatives emerge earlier from GC columns than protiated, thus enabling shorter analysis times. Externally added ²H-, ¹³C-, ¹⁵N and ¹⁸O-isotopologs for use as internal standards undergo similar changes during derivatization, extraction by organic solvents, ionization in the ion-source of GC–MS apparatus and have almost identical retention times with the analytes. Due to selective analytical derivatization, almost all classes of endogenous and exogenous low-molecular-mass analytes, including drugs and inorganic anions such as nitrite, nitrate, carbonate, and (pseudo)halogenides, become accessible to quantitative GC–MS and GC–MS/MS analysis. Thanks the high sensitivity of quantitative analytical methods based on GC–MS and GC–MS/MS, very low amounts of perfluorinated derivatization reagents are consumed. In consideration of the enormously high global warming potential (GWP) of F-containing derivatization reagents, this article discussed a potential abandonment of the use of perfluorinated reagents and their replacement by F-free reagents in GC–MS and GC–MS/MS.