Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometric Analysis of Cellular Glycerophospholipids Enabled by Multiplexed Solvent Dependent Analyte−Matrix Interactions

Abstract

A matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) based approach was developed for the rapid analyses of cellular glycerophospholipids. Through multiplexed solvent-enabled optimization of analyte-matrix interactions during the crystallization process, over a 30-fold increase in S/N was achieved using 9-aminoacridine as matrix. The linearity of response (r 2 =0.99) and dynamic range of this method (over 2 orders of magnitude) were excellent. Moreover, through multiplexing ionization conditions by generating suites of different analytematrix interactions in the absence or presence of different alkali metal cations in the matrix, discrete lipid classes were highly and selectively ionized under different conditions resulting in the de facto resolution of lipid classes without chromatography. The resultant decreases in spectral complexity facilitated tandem mass spectrometric analysis through high energy fragmentation of lithiated molecular ions that typically resulted in informative fragment ions. Anionic phospholipids were also detected as singly negatively charged species that could be fragmented using MALDI tandem mass spectrometry leading to structural assignments. Collectively, these results identify a rapid, sensitive and highly informative MALDI-TOF MS approach for analysis of cellular glycerophospholipids directly from extracts of mammalian tissues without the need for prior chromatographic separation.

Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

“…A mixture of 5 l of acyl CoA extract and 5 l of 9-aminoacridine solution [10 mg of 9-AA/ml in acetone/methanol (98:2, v/v)] was spotted on a MALDI plate and analyzed using a MALDI-TOF mass spectrometer ( 34 ). Quantitative analyses of acyl CoA species by MALDI-TOF-MS with 9-aminoacridine as matrix were similarly assessed as previously described ( 35,36 ) tions we use a timestep of ⌬ t ‫ف‬ 0.05-0.15. Whenever practical, a larger value of ⌬ t is used to reduce the simulation computation time.…”

Collision-induced dissociation of doubly-charged barium-cationized lipids generated from liquid samples by atmospheric pressure matrix-assisted laser desorption/ionization provides structurally diagnostic product ions

“…Far more information was obtained with lithium adducts, where products of the neutral loss of one or the other fatty acid were detected. Lithium and the other Group 1 metals have been used in the literature for structural investigations [10][11][12][13][14], although their utility in obtaining double bond information from lipids typically requires multiple stages of MS/MS and is based on neutral loss rather than direct detection of product ions [14,15].…”

Selective or Class-wide Mass Fingerprinting of Phosphatidylcholines and Cerebrosides from Lipid Mixtures by MALDI Mass Spectrometry

“…However, PEs were easily detected from crude lipid extracts if para-nitroaniline (PNA) or 9-aminoacridine (9-AA) was used as a matrix. 3,9 In addition, inorganic matrices were also employed for this purpose. For example, colloidal graphite and gold nanoparticle matrices were shown to selectively enhance ion signals of cerebrosides (Cers), a group of glycosphingolipids, from brain tissues and lipid extracts.…”