Mass spectral fragmentation of perfluoroacyl derivatives of half nitrogen mustards for their detection by gas chromatography/mass spectrometry

Abstract

Rationale:Analytical methods for the detection and identification of half nitrogen mustards (halfNMs), i.e., partially hydrolyzed products of nitrogen mustards (pHpNMs), using silyl derivatives are often associated with low sensitivity and selectivity. In order to overcome these limitations, the derivatization of halfNMs was performed using perfluoroacylation.Methods: Two efficient derivatization techniques using trifluoroacetyl (TFA) and heptafluorobutyryl (HFB) groups were developed for the unambiguous identification of halfNMs. A mass spectral database was generated by performing gas chromatography/electron ionization mass spectrometry (GC/EI-MS) and gas chromatography/positive chemical ionization mass spectrometry (GC/PCI-MS). The fragmentation pathways were studied by tandem mass spectrometry (MS/MS) in both EI and PCI mode. Results:The EI-MS spectra of the TFA and HFB derivatives of halfNMs contain intense molecular ions and fragment ions, thus making perfluoroacylation preferable to silylation. In addition, the background-free chromatogram obtained using these derivatives provides unambiguous identification of these compounds in blind samples. The structures of the fragment ions were postulated, and the sources of significant ions were traced by performing MS/MS precursor ion scans. In the PCI-MS spectra, along with the protonated molecule, significant peaks due to neutral losses of HF, HCl, CH 3 Cl and CF 3 COOH were observed.Conclusions: This is the first report of the elucidation of the fragmentation pathways of perfluoroacyl derivatives of halfNMs. The complementary GC/PCI-MS and GC/PCI-MS/MS data will be helpful in the identification of unknown metabolites in a fast and reliable fashion.

Fluoride derivatization-enabled sensitive and simultaneous detection of biomarkers for nitrogen mustard in human plasma and urine via gas chromatography tandem mass spectrometry

“…Fluoride derivatization has been widely applied in the retrospective detection of biomarkers of CWAs, such as alkyl alkylphosphonic acid or TDG. 34 However, fluoride derivative techniques have been rarely used in the analysis of NM exposure. Pentafluorobenzoyl chloride was applied as the derivatization regent in previous research with liquid chromatography-tandem mass spectrometry.…”

Practical benzylation of N,N‐substituted ethanolamines related to chemical warfare agents for analysis and detection by electron ionization gas chromatography–mass spectrometry

“…To partially circumvent this issue, a variety of derivatization methods aimed at the conversion of these polar compounds into species possessing superior GC profiles than those of the starting materials have been devised. Specifically, for ethanolamines, some of these methods have involved silylation using BSTFA [14,15], MTBSTFA [16], or the NMI-mediated activation protocol [17,22], as well as equally efficient fluorinations in the form of trifluoroacetyl and heptafluorobutyryl tags [23][24][25]. Even though silylation and acylation are efficient at providing derivatives for N,N-disubstituted ethanolamines, these derivatives are prone to hydrolysis under slightly basic conditions (pH ~ 8-9) unless the amount of steric hindrance on these tags is greatly increased [26].…”

Development of a method for the derivatization of ethanolamines and its application to sand samples

“…Chromatograms of the trifluoroacetylated ethanolamines spiked with TBP are depicted in Fig 4 . The retention indices of the derivatized analytes together with the EI-MS data (the most abundant fragment ions) are given in Table IV. Perfluoroacylation was by Chandra et al 16 tested in the derivatization of half-nitrogen mustards to determine fragmentation pathways. When compared to silylation under similar conditions,15 perfluoroacylation was preferred as the derivatization technique for half-nitrogen mustards due to more intense O n L i n e F i r s t molecular ion peaks.…”

“…Methods for sample-applied derivatization of partially hydrolyzed nitrogen mustards were created using silylation, 15 trifluoroacetylation using TFAI and heptafluorobutyrylation. 16 In the last case, better results were obtained in comparison to silylation. Formation of fluorinated derivatives is recommended also for GC coupled with Fourier transform infrared spectrometry (FTIR) analysis because of the high absorptivity of these derivatives in IR spectrum.…”