Identification of the carboxylic acid functionality by using electrospray ionization and ion-molecule reactions in a modified linear quadrupole ion trap mass spectrometer.
ABSTRACT A mass spectrometric method has been developed for the identification of the carboxylic acid functional group in analytes evaporated and ionized by electrospray ionization (ESI). This method is based on gas-phase ion-molecule reactions of ammoniated ([M + NH4]+) and sodiated ([M + Na]+) analyte molecules with trimethyl borate (TMB) in a modified linear quadrupole ion trap mass spectrometer. The diagnostic reaction involves addition of the deprotonated analyte to TMB followed by the elimination of methanol. A variety of analytes with different func-tionalities were examined, and this reaction was only observed for molecules containing the carboxylic acid functionality. The selectivity of the reaction is attributed to the acidic hydrogen present in the carboxylic acid group, which provides the proton necessary for the elimination of methanol. The diagnostic products are easily identified based on the m/z value of the product ion, which is 72 Th (thomson) greater than the m/z value of the charged analyte, and also by the character-istic isotope pattern of boron. The applicability of this method for pharmaceutical analysis was demonstrated for three nonsteroidal anti-inflammatory drugs: ibuprofen, naproxen, and ketoprofen.
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ABSTRACT: We report here an automated method for the identification of N-oxide functional groups in drug metabolites by using the combination of liquid chromatography/tandem mass spectrometry (LC/MS(n)) based on ion-molecule reactions and collision-activated dissociation (CAD). Data-dependent acquisition, which has been readily utilized for metabolite characterization using CAD-based methods, is adapted for use with ion-molecule reaction-based tandem mass spectrometry by careful choice of select experimental parameters. Two different experiments utilizing ion-molecule reactions are demonstrated, data-dependent neutral gain MS(3) and data-dependent neutral gain pseudo-MS(3), both of which generate functional group selective mass spectral data in a single experiment and facilitate increased throughput in structural elucidation of unknown mixture components. Initial results have been generated by using an LC/MS(n) method based on ion-molecule reactions developed earlier for the identification of the N-oxide functional group in pharmaceutical samples, a notoriously difficult functional group to identify via CAD alone. Since commercial software and straightforward, external instrument modification are used, these experiments are readily adaptable to the industrial pharmaceutical laboratory.Journal of the American Society for Mass Spectrometry 01/2010; 21(4):559-63. · 3.59 Impact Factor
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ABSTRACT: A mass spectrometric method has been delineated for the identification of the epoxide functionalities in unknown monofunctional analytes. This method utilizes gas-phase ion/molecule reactions of protonated analytes with neutral trimethyl borate (TMB) followed by collision-activated dissociation (CAD) in an ion trapping mass spectrometer (tested for a Fourier-transform ion cyclotron resonance and a linear quadrupole ion trap). The ion/molecule reaction involves proton transfer from the protonated analyte to TMB, followed by addition of the analyte to TMB and elimination of methanol. Based on literature, this reaction allows the general identification of oxygen-containing analytes. Vinyl and phenyl epoxides can be differentiated from other oxygen-containing analytes, including other epoxides, based on the loss of a second methanol molecule upon CAD of the addition/methanol elimination product. The only other analytes found to undergo this elimination are some amides but they also lose O = B-R (R = group bound to carbonyl), which allows their identification. On the other hand, other epoxides can be differentiated from vinyl and phenyl epoxides and from other monofunctional analytes based on the loss of (CH(3)O)(2)BOH or formation of protonated (CH(3)O)(2)BOH upon CAD of the addition/methanol elimination product. For propylene oxide and 2,3-dimethyloxirane, the (CH(3)O)(2)BOH fragment is more basic than the hydrocarbon fragment, and the diagnostic ion (CH(3)O)(2)BOH (2) (+) is formed. These reactions involve opening of the epoxide ring. The only other analytes found to undergo (CH(3)O)(2)BOH elimination are carboxylic acids, but they can be differentiated from the rest based on several published ion/molecule reaction methods. Similar results were obtained in the Fourier-transform ion cyclotron resonance and linear quadrupole ion trap mass spectrometer.Journal of the American Society for Mass Spectrometry 01/2012; 23(1):12-22. · 3.59 Impact Factor
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ABSTRACT: Liquid chromatography coupled to mass spectrometry (MS) with electrospray ionization (ESI) is one of analytical techniques to obtain accurate results of low molecular weight aromatic compounds in biological samples of different origin. The interpretations of mass spectra of these aromatic compounds in the negative spectra registered in the full scan MS mode may be uneasy due to presence of deprotonated molecules [M-H](-) from different co-eluting entities, fragment ions created after the break-up of precursor ions and also ions representing modified molecules clusters. Thus, the first aim of this study was to evaluate general parameters during analysis performed in the full scan MS or MS/MS mode. Secondly, to set general fragmentation rules for aromatic compounds and entities in a complex biological matrix. We established that different groups of low molecular weight phenolic acids form unique adduct ions and additionally registration LC/MS/MS spectra with two different collision energies may allow for differentiating isomeric or isobaric molecules. These findings together with some general fragmentation rules can facilitate identifications of aromatic acids as we outlined in the sample of cold-pressed rose-hip oil and lupine leaves extract.Journal of Chromatography B. 01/2014;