Defluorination in Gas Chromatography-Mass Spectrometry in the Negative-Ion Chemical Ionization Mode †

The element fluorine (F) and its organic compounds possess exceptional physicochemical properties and play many important roles in various fields of human life including analytical chemistry and climate science due to their high global warming potential (GWP). This paper deals with the unique role of fluorine in the field of mass spectrometry, especially with the phenomenon of defluorination in gas chromatography-mass spectrometry (GC-MS) under negative-ion chemical ionization (NICI) conditions. Steroidal drugs such as dexamethasone and flumethasone contain very few F atoms incorporated by organic synthesis. Endogenous organic substances do not contain F atoms. Their derivatization with fluorinated organic reagents such as pentafluorobenzyl (PFB) bromide and perfluorinated derivatization reagents such as pentafluoropropionic (PFP) anhydride introduces 10 to 20 F atoms into endogenous low-molecular-mass molecules. The present study reexamined published GC-NICI-MS mass spectra of F-containing drugs and of PFB and PFP derivatives of different classes of endogenous molecules. Such mass spectra often contain several in part intense ions that differ in their mass-to-charge (m/z) values by 20 due to neutral loss of HF molecules. Elimination of HF, i.e., the intramolecular defluorination, in GC-NICI-MS is accompanied with the formation of intramolecular N–C, C–C and C=C bonds with uncommon structures. In derivatives of drugs with intrinsic F atoms defluorination occurs between adjacent groups. In endogenous molecules such as amino acids with extrinsic F atoms, defluorination takes place between remote groups. Apparently, defluorination proceeds without the participation of external electrons such as the secondary electrons formed in the ion source of GC-MS instruments under NICI conditions from the ionization of reagent gases such as methane. A possible mechanism of the intramolecular defluorination in GC-NICI-MS could be intramolecular redox reactions because of a “gradient” of oxidation numbers between F-carrying C atoms with higher oxidation numbers and H-carrying C atoms with lower oxidation numbers in organic analytes. Low-extent defluorination occurs in H-free substances such as the tuning substance perfluorotributylamine (PFTBA, C12F27N), due to neutral loss of F2 (38 Da). It is assumed that the defluorination in PFTBA proceeds between the terminal CF3 and the adjacent CF2 groups which have higher and lower oxidation numbers on the C atoms, respectively. Considerably higher-extent of defluorination occurs in methyl ester pentafluoropropionyl derivatives of amino acids; defluorination occurs between the CF3 group of the PFP residue and the N atom of the α-amine group. In 60% of the 25 investigated amino acids, the most intensive ions in the GC-NICI-MS mass spectra were due to [M − 1 × HF]−, followed by 12% due to [M − 2 × HF]−, and 4% due to [M − 3 × HF]−. The paper discusses potential factors, including chemical structures of the fluorinated analytes and experimental conditions in the ion source block, such as electron energy, emission current, and temperature, that may influence the degree of defluorination. Based on the results of the present examination, the authors suggest GC-NICI-MS investigations of the defluorination of perfluorooctane sulfonic acid (PFOS) by using F-free decanoyl chloride as model derivatization reagent to find out optimum experimental conditions for maximum defluorination.