Adduct formation in electrospray ionization. Part 1: Common acidic pharmaceuticals

Abstract

This study focuses on pseudo-molecular ion formation in electrospray ionization mass spectrometry (ESI-MS) of six anti-inflammatory pharmaceuticals with similar functionality. The formation of particular pseudo-molecular ions depends on ion affinity and molecular structure of the analyte as well as the solvent/buffer conditions used. Six common anti-inflammatory agents are mixed 1:1 with six different acetonitrile/aqueous buffer solutions at varying concentrations. The analytes are ibuprofen, carprofen, naproxen, ketoprofen, flurbiprofen, and fenoprofen. The pK a and surface activity of the analytes and the pH, concentration, and type of the solvent system strongly affect the ions formed [1,2]. The additives are common liquid chromatography (LC) mobile phase modifiers. The spectral intensities of three major pseudo-molecular ions were measured by flow injection analysis ESI-MS. The ions studied correspond to the deprotonated molecular ion ([M - H] - ), a deprotonated dimer ion ([2M - H] - ), and a deprotonated dimer ion pair with sodium ([2M - 2H+Na] - ). These ions were chosen due to their high relative abundance in a majority of the spectra. The pKa of the analytes studied range from 4.1 to 4.4, due to their aromatic acetic acid moiety. The common carboxylic acid group facilitates ESI of the compounds in the negative ionization mode. The changes in molecular structure of these model compounds allows for a wide variety of solution interactions. Some analytes are effectively declustered under the set conditions creating an intense [M - H] - peak, whereas others prefer to form dimers or complexes with sodium.