Strategies for structure elucidation using Ultrafast Mass Spectrometry (UFMS): Using nMS2 as an alternative to MS3

Ultrafast Mass Spectrometry (UFMS) is an adaptation of quadrupole mass filtering that provides Ultrafast scanning (15000 ?/sec) and Ultrafast polarity switching (15 msec). Importantly, the scanning speed does not result in the mass axis displacement or a loss of sensitivity for constant dwell time and still maintains 0.1 ? mass definition (10 points per 1 ? rather than interpolated masses.) By necessity, UFMS must operate on all stages of the ion trajectory (pre-filters, Q1, collision cell and Q3) and support negligible cross-talk.

We have applied UFMS to generate multiple product ion spectra (PIS) across a UHPLC peak with CID at varying energies. The nMS² approach yields an array of MSMS spectra derived from the same parent ion but exhibiting mechanistically distinct fragment ions. Typically, we have driven simple neutral losses at low collision energy (10 V potential difference across the collision cell), fission of pendant moieties (30-50 V) and more significant aromatic rearrangements and formation of fused cyclic structures at higher collision energies. We have also tracked halogenated fragments of metoclopramide with parallel PIS from the MH+2 across the collision energy range. UFMS has enabled on-the-fly detection and identification of novel compounds (e.g. metabolites) with arrayed MS2 data.

Unlike MSn, the nMS² approach is not subject to the transfer loss limitations on sensitivity because the same parent ion is selected from the first mass filter rather than from collisional debris.

The use of nMS² in combination with Ultrafast polarity switching allows one or more of the elements in the PIS array to be based on either negative or positive ions and so increases the informing power of the data set. Similarly, nMS² allows the selection of multiple parents (isotopic contributors or co-resident adducts) as well as the fragmentation of products from source induced fragmentation or neutral loss (pseudo-MS³).