Prediction of Adducts on Positive Mode Electrospray Ionization Mass Spectrometry: Proton/Sodium Selectivity in Methanol Solutions

Abstract

We used positive mode electrospray ionization (ESI) mass spectrometry to examine 540 in-house high-resolution mass spectrometry (HRMS) samples that formed an adducted positive ion. Of the 540 samples, the sodium adduct ([M+Na]⁺) was detected in 480 samples, and the protonated molecule ([M+H]⁺) was detected in 92 samples; both [M+Na]⁺ and [M+H]⁺ were detected in 32 samples. No other adduct ions were predominant. The selectivities of these adducts were evaluated by a two-dimensional plot using topological polar surface area (tPSA) and molecular weight. Two predominant trends were observed: [M+H]⁺ converged around tPSA (Ų) = 20 and molecular weight = 250, and the selectivity for [M+Na]⁺ correlated with the tPSA value. These observations were found to be related to the elemental composition of the sample compounds. From the results obtained by positive mode ESI mass spectroscopy under our experimental conditions, predominant trends were observed with respect to adduct selectivity: compounds containing oxygen atom(s) form [M+Na]⁺, and compounds containing nitrogen but not oxygen atom(s) form [M+H]². Based on these trends, we developed the "Nitrogen-Oxygen rule" (NO rule) to predict the adduct formed by a given compound on positive mode ESI. This NO rule provides a guideline to estimate elemental composition using ESI-HRMS with methanol as mobile phase.

Observed adducts on positive mode direct analysis in real time mass spectrometry – Proton/ammonium adduct selectivities of 600-sample in-house chemical library

“…Besides, on comparison with our previous study with regard to adduct selectivity on ESI using the same sample set, [M þ H] þ group of ESI almost overlapped [M þ H] þ group of DART. 17 In contrast, spreading of [M þ H] þ group of DART on a twodimensional scatter plot using the MW and tPSA values were extremely wide. It suggests that DART adduct selectivity is not simply dependent on the elemental composition.…”

“…A chemical library was constructed by collecting samples submitted to our contracted HRMS measurement service. 15,17,18 The library samples were gathered from June 2012 to March 2013, and 611 samples were obtained. The identities of all the compounds in the sample library were confirmed by HRMS using ESI time-of-flight mass spectrometry (a few samples were confirmed using a FAB sector mass spectrometer) with errors of <5 ppm compared with the elemental compositions declared by the clients of the HRMS measurement service.…”

“…The calculation details are given in our previous studies. 15,17 Results and discussion Observed DART adducts for in-house chemical library…”

“…27 In our previous two studies, the molecular polarity was correlated with the ion source applicability and ESI adduct selectivity. 15,17 In this study, tPSA was used as the molecular polarity, and the distributions of the molecular polarities were compared with the MWs for each of the three compound groups (Figure 1). However, clear significant trends were not found.…”

“…6 In order to use the ion source as a complementary ion source of ESI for high-resolution mass spectrometry (HRMS), it is extremely important to know the property of the formation of adducts. 17 However, adduct selectivity of DART has not been investigated in any detail.…”