Effect of Mobile Phase pH on the Electrospray Ionization Efficiency and Qualitative Analysis of Pharmaceuticals in ESI + LC-MS/MS

Abstract

The effect of mobile phase pH on positive ionization process and retention time of nine pharmaceuticals on ultra-performance liquid chromatography-electrospray–tandem mass spectrometry (LC-MS/MS) was discussed. The effective use of high and low mobile phase pH in LC-MS/MS qualitative analyses method was also evaluated by comparing the instrument detection limit, quantification limit, precision, linearity and signal to noise (S/N) under low and high mobile phase pH. In this work, six mobile phase pH that ranged between pH 2 and pH 10 were used to evaluate the effect of the mobile phase pH changes on the ionization process in electrospray ionization. Results revealed that high mobile phase pH ionized more pharmaceuticals molecules and gave a higher signal than low mobile phase pH in positive ionization mode. The results proved that ammonium ion was better as a proton donor in high pH mobile phase than the hydronium ion in acidic mobile phase. The results revealed that the qualitative LC-MS/MS analyses method by using high mobile phase pH has better performance for most analytes in terms of sensitivity, precision, linearity and S/N than the low mobile phase pH.

Study on the separation mechanism of solid‐substrate electrospray ionization mass spectrometry

“…The quantitative relationship between chromatographic retention factor k and retention time t r is shown in Eq. (2) [19], where t 0 is the dead time of a compound. Under the isocratic elution condition, k changes with φ (the proportion of strong elution solvent in the binary mobile phase) satisfying formula [20] (3), where k w is the extrapolated value of k when φ = 0, and S is a constant when only φ is changed.…”

“…The quantitative relationship between chromatographic retention factor k and retention time t r is shown in Eq. (2) [19],…”

Technologies to improve the sensitivity of existing chromatographic methods used for bioanalytical studies

“…Furthermore, they demonstrated that ammonium bicarbonate buffer could result in a greater sensitivity for high pH modifiers compared with ammonium acetate. More recently, Kafeenah, Osman, and Bakar () applied LC–ESI + –MS/MS to evaluate the MS signals of nine drugs under six mobile phases ranging between pH 2 and pH 10. As shown in Figure , MS signals increased significantly when the mobile phase pH was greater than 6 for most analytes.…”

“…MS signals of nine drugs under six mobile phases ranging from pH 2 to pH 10 (retrieved from Kafeenah et al, ) [Colour figure can be viewed at wileyonlinelibrary.com]…”

“…The author points out that much work has been done with small molecules in this area, and the development of 2D-LC methods for the determination of proteins, lipids, nucleosides, and polysaccharides has made big strides from 2010 to 2015. Another review has listed more than 80 2D-LC F I G U R E 1 MS signals of nine drugs under six mobile phases ranging from pH 2 to pH 10 (retrieved from Kafeenah et al, 2019) [Colour figure can be viewed at wileyonlinelibrary. com] applications for pharmaceutical compounds up to 2017.…”