Identification of the Carboxylic Acid Functionality by Using Electrospray Ionization and Ion−Molecule Reactions in a Modified Linear Quadrupole Ion Trap Mass Spectrometer

Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
Analytical Chemistry (Impact Factor: 5.64). 06/2008; 80(9):3416-21. DOI: 10.1021/ac800002h
Source: PubMed


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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    • "[16] [17] [18] The choice of using negative ionization mode in mass spectrometric methods is appropriate for the direct analysis of carboxylic acids due to their acidic nature. [19] [20] However, high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) methods are typically used in positive ion mode to analyze carboxylic acids after their covalent derivatization, [21] [22] [23] [24] because the ionization efficiencies of carboxylic acids in negative ion mode are rather low, [21] [22] and, in addition, the acidic mobile phase additives which are routinely used to improve chromatographic resolution in reversed-phase HPLC separations tend to suppress the negative ionization in ESI- MS. [25] [26] Despite the significant improvement in sensitivity for positive MS detection of carboxylic acids after their derivatization, the covalent derivatization reactions are nonetheless time-consuming and may result in the formation of unwanted side products, [26] which is not good for the rapid detection of samples. Cyclodextrins (CDs) are cyclic oligosaccharides consisting of α-1,4-linked glucose residues. "
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