Think Negative: Finding the Best Electrospray Ionization/MS Mode for Your Analyte

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Separation Science

Background:

• Electrospray ionization (ESI) is a crucial technique in mass spectrometry for analyzing diverse compounds.
• Optimizing ionization conditions, specifically positive versus negative mode, is vital for maximizing sensitivity.
• Current methods lack a unified system for direct comparison of ionization efficiency (IE) across modes.

Purpose of the Study:

• To develop a novel system for directly comparing electrospray ionization efficiency (IE) in positive and negative modes.
• To establish a standardized approach for selecting optimal ionization conditions for enhanced analytical sensitivity.
• To challenge conventional practices by evaluating the sensitivity of positive versus negative ESI modes.

Main Methods:

• Development of a unified IE scale using a reference compound with similar ionization in both positive and negative modes.
• Analysis of 33 diverse compounds capable of ionizing in both positive and negative modes.
• Quantification and comparison of ionization efficiencies across both modes for each compound.

Main Results:

• A novel system successfully enabled direct comparison of IE values across positive and negative ionization modes.
• Negative mode provided superior sensitivity for 46% of the tested compounds, contrary to common assumptions.
• Positive mode was preferred for only 18% of compounds, while 36% showed comparable sensitivity in both modes.

Conclusions:

• The developed unified system effectively allows for the direct comparison of electrospray ionization efficiency across modes.
• Negative ion mode offers superior sensitivity for a significant portion of analytes, necessitating a re-evaluation of standard practices.
• This approach enables informed selection of optimal ionization conditions, enhancing analytical sensitivity and method development.