Analysis of eicosanoids by quadrupole gas chromatography-negative ion chemical ionization-tandem mass spectrometry as pentafluorobenzyl trimethylsilyl derivatives: Naming the Murphy rearrangement

Eicosatetraenoic acid (arachidonic acid) is the precursor of the eicosanoids, which include the prostaglandins (PGs), the leukotrienes (LTs), and the endocannabinoids (ECs). Methods based on GC–MS/MS are the Gold Standard for the quantitative analysis of eicosanoids in biological samples. After extraction and derivatization, biological eicosanoids 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) generates in the ion-source abundant anions due to [M–PFB]⁻. Collision-induced dissociation (CID) of [M–PFB]⁻ in the collision cell generates product ions, which are suitable candidates for specific quantitative analyses in the selected-reaction monitoring (SRM) mode. In this article, we review CID gas-phase reactions of PFB-TMS derivatives of PGs and LTs. The specific CID negative charge-driven intramolecular rearrangement of TMS groups from ether moieties (OTMS) to carboxylate anions [M–PFB]⁻ of PFB-TMS derivatives to form a –COO-TMS ester has been reported for the first time by Robert C. Murphy on PFB-TMS derivatives of 5-hydroxy-eicosanoic acid (HEA) from hydrogenated and desulfurized LTE₄, and saturated LTB₄. We propose to name this specific CID gas-phase reaction the Murphy Rearrangement in honour of R.C. Murphy. The Murphy Rearrangement generates the product ions m/z 253 and m/z 89 from the precursor ion m/z 399 of the PFB-TMS derivative of HEA and neutral loss of 146 Da. We propose to name Murphy-type Rearrangements that were observed for the eicosanoids 8-isoPGF_2α, its 2,3-dinor- and 2,3-dinor-5,6-dihydro-metabolites, the major urinary metabolites (MUM) of F and E prostaglandins, i.e., PGF-MUM and PGE-MUM, respectively, as well as for the CID of m/z 179 [M–PFB]⁻ of the PFB ester of the drug acetylsalicylic acid (aspirin). The Murphy Rearrangement and Murphy-type Rearrangements differ with respect to the rearrangement ion and the subsequent neutral losses and fragmentations. The Murphy-type Rearrangements of PGF-MUM and PGE-MUM includes a specific neutral loss of 198 Da PFBOH due to intramolecular attack of 1- or ω-COO⁻ anions to ω- or 1-COO-PFB esters. Murphy Rearrangements and Murphy-type Rearrangements are best identified by performing CID studies on PFB-TMS derivatives of [1,1-¹⁸O₂]- and [1,ω-¹⁸O₂]-eicosanoids in the NICI mode. Neutral loss of TMS¹⁸OH (92 Da) and PFB¹⁸OH (200 Da) (in dicarboxy-eicosanoids), and formation of a product ion with m/z 91 [TMS¹⁸O]⁻ will indicate Murphy Rearrangements and Murphy-type Rearrangements. Formation of a product ion with m/z 59 (acetate) from the CID of m/z 179 [M–PFB]⁻ of the PFB ester of acetylsalicylic acid will be indicative of a Murphy-type Rearrangement.