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.

Differentiation of Regioisomeric Aromatic Ketocarboxylic Acids by Positive Mode Atmospheric Pressure Chemical Ionization Collision-Activated Dissociation Tandem Mass Spectrometry in a Linear Quadrupole Ion Trap Mass Spectrometer

“…Mass spectrometry (MS) has evolved into an essential tool for the identification of unknown substances in mixtures [8,9]. With the onset of many new ionization methods, such as electrospray ionization (ESI), atmospheric pressure photoionization (APPI), and atmospheric pressure chemical ionization (APCI), MS has become a valuable tool for mixture analyses, especially when combined with high-performance liquid chromatography (HPLC) [10,11].…”

Identification of Epoxide Functionalities in Protonated Monofunctional Analytes by Using Ion/Molecule Reactions and Collision-Activated Dissociation in Different Ion Trap Tandem Mass Spectrometers

“…The only other analytes whose addition/methanol elimination products have been found [22] to fragment by elimination of (CH 3 O) 2 BOH are carboxylic acids (for a possible mechanism, see Scheme 5), but they can be differentiated from all other monofunctional oxygencontaining analytes by various other ion/molecule reactionbased approaches [20,27].…”

“…Other epoxides can be differentiated from vinyl and phenyl epoxides and other oxygen-containing molecules 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 formed upon reaction with TMB. The only other analytes found to fragment via loss of (CH 3 O) 2 BOH are carboxylic acids, which can be differentiated from all other analytes by literature methods [20,27].…”

“…A diagram of the exact manifold used in this research was published by Habicht et al [27]. TMB was introduced into the manifold via a syringe pump maintained at 20 μL/h.…”

“…This study focuses on the distinction of protonated epoxides from other monofunctional oxygen-containing analytes by using ion/molecule reactions followed by CAD in a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer and a commercially available linear quadruple ion trap (LQIT) mass spectrometer that has been modified to allow the introduction of neutral reagents into the ion trap via an external mixing manifold [27]. The results demonstrate that CAD of the addition/methanol elimination products of protonated epoxides formed upon reaction with TMB not only allows distinction of epoxides from other analytes, but vinyl and phenyl epoxides can also be differentiated from other epoxides.…”