How to perform analyses using the "loss of neutral" acquisition mode on a ZenoTOF system with SCIEX OS software?

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How-to-perform-analyses-using-the-loss-of-neutral-acquisition-mode-on-a-ZenoTOF_en_US

In MS/MS mass spectrometry, a neutral loss refers to the loss of a neutral molecule during the fragmentation of a precursor ion. This results in a mass difference (Δm) between the precursor and a fragment ion. Certain neutral losses are characteristic of specific functional groups (e.g., H₂O, CO₂, NH₃…). Thus, tracking a neutral loss allows you to: Deduce the chemical functions, increase confidence in identification, sort and recognize families of compounds in complex analyses. This article explains how to perform neutral loss analysis on a ZenoTOF system with SCIEX OS software.

For research use only. Not for use in diagnostic procedures.

Answer

Procedure to create a neutral loss method with a ZenoTOF system:

1) Create an IDA method.

2) In the IDA criteria dropdown list, select "All," which will activate the Neutral Loss option (ensure that advanced criteria are selected to display it).

3) Check the Neutral Loss box and click the hyperlink to define the minimum and maximum collision energies to apply. Select the mass difference to apply for neutral loss.

Here is an example configuration :

Additional information:

As opposed to the MRMHR experiments, which use Zeno trapping, the IDA experiments for neutral loss do not use Zeno trapping. Consequently, the signal difference is 5 to 10 times lower for neutral loss—as expected without Zeno—compared to the MRMHR experiment with Zeno enabled.
You can increase the accumulation time for the NL experiment and reduce the MS/MS portion of this method to increase the signal for the NL experiment.

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2026-04-14

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Software - SCIEX OS software; Mass spectrometry - TOF TOF systems; Category - LCMS; Sub category - Operation