High-Resolution Ion Mobility Spectrometry Mass Spectrometry for Isomeric Separation of Prostanoids after Girard's reagent T Derivatization

L Lamont, D Hadavi, A P Bowman, B Flinders, D Cooper-Shepherd, M Palmer, J Jordens, Y Mengerink, M Honing, J Langridge, T Porta Siegel, R J Vreeken*, R M A Heeren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


RATIONALE: Isomeric separation of prostanoids is often a challenge and requires chromatography and time-consuming sample preparation. Multiple prostanoid isomers have distinct in vivo functions crucial to understand the inflammation process, including prostaglandins E2 (PGE2 ) and D2 (PGD2 ). High-resolution Ion Mobility Spectrometry (IMS) based on linear ion transport in low-to-moderate electric fields and nonlinear ion transport in strong electric fields emerges as a broad approach for rapid separations prior to mass spectrometry (MS).

METHODS: Derivatization with Girard's reagent T (GT) was used to overcome inefficient ionization of prostanoids in negative ionization mode due to poor deprotonation of the carboxylic acid group. Three high-resolution IMS techniques including linear cyclic IMS (cIMS), linear Trapped IMS (TIMS), and nonlinear high-Field Asymmetric Waveform IMS (FAIMS) were compared for the isomeric separation and endogenous detection of prostanoids present in intestinal tissue.

RESULTS: Direct infusion of GT derivatized prostanoids proved to increase the ionization efficiency in positive ionization mode by a factor of >10, which enabled detection of these molecules in endogenous concentration levels. The high-resolution IMS comparison revealed its potential for rapid isomeric analysis of biologically relevant prostanoids. Strengths and weaknesses of both linear and nonlinear IMS were discussed. Endogenous prostanoid detection in intestinal tissue extracts demonstrated the applicability of our approach in biomedical research.

CONCLUSIONS: The applied derivatization strategy offers high sensitivity and improved stereoisomeric separation for screening of complex biological systems. The high-resolution IMS comparison indicated that the best sensitivity and resolution are achieved by linear and nonlinear IMS, respectively.

Original languageEnglish
Article numbere9439
Number of pages10
JournalRapid Communications in Mass Spectrometry
Issue number5
Early online date22 Nov 2022
Publication statusPublished - 15 Mar 2023


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