Competitive homolytic and heterolytic decomposition pathways of gas-phase negative ions generated from aminobenzoate esters.

An alkyl-radical loss and an alkene loss are two competitive fragmentation pathways that deprotonated aminobenzoate esters undergo upon activation under mass spectrometric conditions. For the meta and para isomers, the alkyl-radical loss by a homolytic cleavage of the alkyl-oxygen bond of the ester moiety is the predominant fragmentation pathway, while the contribution from the alkene elimination by a heterolytic pathway is less significant. In contrast, owing to a pronounced charge-mediated ortho effect, the alkene loss becomes the predominant pathway for the ortho isomers of ethyl and higher esters. Results from isotope-labeled compounds confirmed that the alkene loss proceeds by a specific γ-hydrogen transfer mechanism that resembles the McLafferty rearrangement for radical cations. Even for the para compounds, if the alkoxide moiety bears structural motifs required for the elimination of a more stable alkene molecule, the heterolytic pathway becomes the predominant pathway. For example, in the spectrum of deprotonated 2-phenylethyl 4-aminobenzoate, m/z 136 peak is the base peak because the alkene eliminated is styrene. Owing to the fact that all deprotonated aminobenzoate esters, irrespective of the size of the alkoxy group, upon activation fragment to form an m/z 135 ion, aminobenzoate esters in mixtures can be quantified by precursor ion discovery mass spectrometric experiments.

A distonic radical-ion for detection of traces of adventitious molecular oxygen (O2) in collision gases used in tandem mass spectrometers.

We describe a diagnostic ion that enables rapid semiquantitative evaluation of the degree of oxygen contamination in the collision gases used in tandem mass spectrometers. Upon collision-induced dissociation (CID), the m/z 359 positive ion generated from the analgesic etoricoxib undergoes a facile loss of a methyl sulfone radical [(•)SO(2)(CH(3)); 79-Da] to produce a distonic radical cation of m/z 280. The product-ion spectrum of this m/z 280 ion, recorded under low-energy activation on tandem-in-space QqQ or QqTof mass spectrometers using nitrogen from a generator as the collision gas, or tandem-in-time ion-trap (LCQ, LTQ) mass spectrometers using purified helium as the buffer gas, showed two unexpected peaks at m/z 312 and 295. This enigmatic m/z 312 ion, which bears a mass-to-charge ratio higher than that of the precursor ion, represented an addition of molecular oxygen (O(2)) to the precursor ion. The exceptional affinity of the m/z 280 radical cation towards oxygen was deployed to develop a method to determine the oxygen content in collision gases.

Direct detection and identification of active pharmaceutical ingredients in intact tablets by helium plasma ionization (HePI) mass spectrometry.

A simple modification converts an electrospray ion source to an ambient-pressure helium plasma ionization source without the need of additional expensive hardware. Peaks for active ingredients were observed in the spectra recorded from intact pharmaceutical tablets placed in this source. A flow of heated nitrogen was used to thermally desorb analytes to gas phase. The desorption temperatures were sometimes as low as 50 °C. For example, negative-ion spectra recorded from an aspirin tablet showed peaks at m/z 137 (salicylate anion) and 179 (acetylsalicylate anion) which were absent in the background spectra. The overall ion intensity increased as the desorption gas temperature was elevated. Within the same acquisition experiment, both positive- and negative-ion signals for acetaminophen were recorded from volatiles emanating from Tylenol tablets by switching the polarity of the capillary back and forth. Moreover, different preparations of acetaminophen tablets could be distinguished by their ion-intensity thermograms.

Gas-phase fragmentations of anions derived from N-phenyl benzenesulfonamides.

In addition to the well-known SO2 loss, there are several additional fragmentation pathways that gas-phase anions derived from N-phenyl benzenesulfonamides and its derivatives undergo upon collisional activation. For example, N-phenyl benzenesulfonamide fragments to form an anilide anion (m/z 92) by a mechanism in which a hydrogen atom from the ortho position of the benzenesulfonamide moiety is specifically transferred to the charge center. Moreover, after the initial SO2 elimination, the product ion formed undergoes primarily, an inter-annular H2 loss to form a carbazolide anion (m/z 166) because the competing intra-annular H2 loss is significantly less energetically favorable. Results from tandem mass spectrometric experiments conducted with deuterium-labeled compounds confirmed that the inter-ring mechanism is the preferred pathway. Furthermore, N-phenyl benzenesulfonamide and its derivatives also undergo a phenyl radical loss to form a radical ion with a mass-to-charge ratio of 155, which is in violation of the so-called "even-electron rule."

Formation of the bisulfite anion (HSO(3) (-) , m/z 81) upon collision-induced dissociation of anions derived from organic sulfonic acids.

In the negative-ion collision-induced dissociation mass spectra of most organic sulfonates, the base peak is observed at m/z 80 for the sulfur trioxide radical anion (SO(3) (-·) ). In contrast, the product-ion spectra of a few sulfonates, such as cysteic acid, aminomethanesulfonate, and 2-phenylethanesulfonate, show the base peak at m/z 81 for the bisulfite anion (HSO(3) (-) ). An investigation with an extensive variety of sulfonates revealed that the presence of a hydrogen atom at the ß-position relative to the sulfur atom is a prerequisite for the formation of the bisulfite anion. The formation of HSO(3) (-) is highly favored when the atom at the ß-position is nitrogen, or the leaving neutral species is a highly conjugated molecule such as styrene or acrylic acid. Deuterium-exchange experiments with aminomethanesulfonate demonstrated that the hydrogen for HSO(3) (-) formation is transferred from the ß-position. The presence of a peak at m/z 80 in the spectrum of 2-sulfoacetic acid, in contrast to a peak at m/z 81 in that of 3-sulfopropanoic acid, corroborated the proposed hydrogen transfer mechanism. For diacidic compounds, such as 4-sulfobutanoic acid and cysteic acid, the m/z 81 ion can be formed by an alternative mechanism, in which the negative charge of the carboxylate moiety attacks the α-carbon relative to the sulfur atom. Experiments conducted with deuterium-exchanged and deuterium-labeled analogs of sulfocarboxylic acids demonstrated that the formation of the bisulfite anion resulted either from a hydrogen transfer from the ß-carbon, or from a direct attack by the carboxylate moiety on the α-carbon.

Ortho effect in electron ionization mass spectrometry of N-acylanilines bearing a proximal halo substituent.

Electron ionization (EI) mass spectra are not very helpful for characterizing ortho, meta, and para isomers of underivatized haloanilines since their spectra are virtually identical. In contrast, when the amino group of chloro-, bromo-, or iodoanilines is transformed to an N-formyl, N-acetyl, or N-benzoyl derivative, the spectra of the derivatives reveal a highly dramatic loss of a halogen radical, instead of an HX elimination usually expected from an "ortho effect." For example, the spectra of N-formyl, N-acetyl, and N-benzoyl derivatives of ortho isomers of chloro-, bromo-, and iodoanilines show a very prominent peak at m/z 120, 134, and 196, respectively, for the loss of the corresponding halogen atom.