RationaleSilver doping of electrospray is known to increase the abundance of olefinic compounds detected by mass spectrometry. While demonstrated in targeted experiments, this has yet to be investigated in an untargeted study. Utilizing infrared matrix‐assisted laser desorption electrospray ionization mass spectrometry imaging (IR‐MALDESI‐MSI), an untargeted lipidomics experiment on mouse liver was performed to evaluate the advantages of silver‐doped electrospray.Methods10 ppm silver nitrate was doped into the IR‐MALDESI solvent consisting of 60% acetonitrile and 0.2% formic acid. Using an Orbitrap mass spectrometer in positive ionization mode, MSI was performed, analyzing from m/z 150 to m/z 2000 to capture all lipids with potential silver adducts. The lipids detected in the control and silver‐doped electrosprays were compared by annotating using the LIPID MAPS Structural Database and eliminating false positives using the metabolite annotation confidence score.ResultsSilver‐doped electrospray allowed for the detection of such ions of lipid molecules as [M + H]⁺ or [M + NH₄]⁺ and as [M + Ag]⁺. Among the ions seen as [M + H]⁺ or [M + NH₄]⁺, the signal was comparable between the control and silver‐doped electrosprays. The silver‐doped electrospray led to a 10% increase in the number of detected lipids, all of which contained a bay region increasing the interaction between silver and alkenes. Silver preferentially interacted with lipids that did not contain hard bases such as phosphates.ConclusionsSilver‐doped electrospray enabled detection of 10% more olefinic lipids, all containing bay regions in their putative structures. This technique is valuable for detecting previously unobserved lipids that have the potential to form bay regions, namely fatty acyls, glycerolipids, prenol lipids, and polyketides.