Collision-Induced Gas-Phase Reactions of PFB-TMS Derivatives of F2-P s in Quadrupole GC-NICI-MS/MS: A Mini-Review and a Meta-Analysis

Arachidonic acid (eicosatetraenoic acid) is the precursor of the eicosanoids, which include prostaglandins (PG). Methods based on GC-MS/MS are the Gold Standard for the quantitative analysis of eicosanoids in biological samples. After extraction and derivatization, biological F2-prostaglandins are analyzed on quadrupole GC-MS/MS apparatus as pentafluorobenzyl (PFB) ester trimethylsilyl (TMS) ether derivatives, i.e., PFB-TMS. Negative-ion chemical ionization (NICI) in the ion source generates abundant anions due to [M-PFB]−, which are detected in the selected ion monitoring (SIM) mode. Collision-induced dissociation (CID) of [M-PFB]− in the collision cell generates numerous product ions, which are suitable candidates for quantitative analyses in the selected reaction monitoring (SRM) mode. In this article, we report on investigations of gas-phase reactions of PFB-TMS derivatives of F2-prostaglandins, which consist of PGF2α, 8-iso-PGF2α, and up to 62 further isomers, known as the F2-isoprostanes. We performed a meta-analysis of previously reported CID mass spectra (32 eV) of PFB-(TMS)3 of seven chemically closely related isomeric F2-prostaglandins of the 15-F2t-IsoP type. This unique dataset contains 19 product ions generated by CID of the common precursor at m/z 569 [M-PFB]− in the m/z range of 150–600. All isomers produced the same product ions, which, however, greatly differed in their intensity. Principal Component Analysis (PCA) and Receiver Operating Characteristic (ROC) Analysis (ROCA) were performed. Two compounds, i.e., 8-iso-9β,11α-PGF2α and 9α,11β-PGF2α, and two product ions, i.e., m/z 299 [M-PFB-3×TMSOH]− and m/z 215 [M-PFB-3×TMSOH-C4H8-C2H4]−, were noticeable. ROCA revealed the highest disagreement between PGF2α and 8-iso-9β,11α-PGF2α (AUC = 0.7075 ± 0.0834, p = 0.0248). PCA and ROCA are of limited value in the GC-MS/MS of closely chemically related F2-prostaglandins. Fragmentation mechanisms were proposed for the formation of all 19 product ions generated by CID of common precursor anions due to [M-PFB]−.