Acetonitrile/water gas‐phase reaction products observed by use of atmospheric pressure chemical ionization: adducts formed with sulfonamides

Abstract

Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are the two most common mass spectrometric ionization methods used in the pharmaceutical industry. However, APCI analysis can sometimes lead to ambiguity in compound characterization and quantitation due to gas-phase reactions occurring between acetonitrile and water in the plasma, and between these plasma-generated compounds and the analyte. During the analysis of various sultams and sulfonamides we observed signals corresponding to m/z [M+44](+) and [M+60](+). Various solvent conditions and collisionally activated dissociation MS(n) experiments revealed that under the high-energy plasma conditions of APCI, the acetonitrile/water solvent mixture reacts undergoing acid-catalyzed hydrolysis producing acetamide, 59 Da. Further, the highly reactive 43 Da species ethanimine is also produced. These two compounds, normally not observed in APCI analysis, are stabilized by the sulfonamide and appear as adduct species in the mass spectra. The sulfone oxygens and the lone pair of electrons on the amide nitrogen play a role in stabilizing this adduct.

Direct determination of dialkyl phosphates by strong anion‐exchange liquid chromatography/atmospheric pressure chemical ionization mass spectrometry using a quadrupole ion trap instrument

“…For example, reduction of nitro compounds and aromatic amines has been observed 24, 25. Ion molecule reactions with acetone,26 acetonitrile,27, 28 and nitrogen29 also occur in APCI plasmas. In the case of nitro reduction the plasma is surface‐assisted, and can be minimized by avoiding protic solvents, by the use of clean heated probe liners and, surprisingly, the use of higher heated nebulizer temperatures (>500°C).…”

On-line H/D exchange LC–MS strategy for structural elucidation of pharmaceutical impurities

“…Nevertheless, it has been shown that gas-phase reduction of ACN in the presence of [16,17]. Data interpretation of these unusual ions may require additional experimental data while H/D exchange methodologies can be applied to confirm these gas-phase reaction products.…”

Liquid chromatography‐mass spectrometry and related techniques for purity assessment in early drug discovery

“…One of the reasons for this finding is the practical problems observed in the corona needle when ACN is used as organic modifier, which contributes to lower ionisation efficiency. Besides, Ross et al [17] have recently reported that APCI analyses sometimes lead to ambiguity on compound characterisation and quantification since a new reactive species has been observed for certain classes of compounds when ACN/ water is used as the solvent system. At present, ESI mode is being most widely used in conjunction with LC in our research laboratories.…”