Tsikas Dimitrios
Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, 30623 Hannover, Germany.
J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Sep 14;1267:124794. doi: 10.1016/j.jchromb.2025.124794.
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 LTE, and saturated LTB. 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, 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-O]- and [1,ω-O]-eicosanoids in the NICI mode. Neutral loss of TMSOH (92 Da) and PFBOH (200 Da) (in dicarboxy-eicosanoids), and formation of a product ion with m/z 91 [TMSO] 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.
二十碳四烯酸（花生四烯酸）是类二十烷酸的前体，类二十烷酸包括前列腺素（PGs）、白三烯（LTs）和内源性大麻素（ECs）。基于气相色谱 - 串联质谱（GC-MS/MS）的方法是生物样品中类二十烷酸定量分析的金标准。经过提取和衍生化后，生物类二十烷酸在四极杆GC-MS/MS仪器上作为五氟苄基（PFB）酯三甲基硅烷基（TMS）醚衍生物，即PFB-TMS进行分析。负离子化学电离（NICI）在离子源中由于[M - PFB]产生大量阴离子。碰撞池中的[M - PFB]的碰撞诱导解离（CID）产生产物离子，这些产物离子是选择反应监测（SRM）模式下特定定量分析的合适候选物。在本文中，我们综述了PGs和LTs的PFB-TMS衍生物的CID气相反应。罗伯特·C·墨菲首次报道了PFB-TMS衍生物中TMS基团从醚部分（OTMS）到PFB-TMS衍生物的羧酸根阴离子[M - PFB]的特定CID负电荷驱动的分子内重排，形成 -COO-TMS酯，该衍生物来自氢化和脱硫的LTE以及饱和LTB的5-羟基二十烷酸（HEA）的PFB-TMS衍生物。我们提议将这种特定的CID气相反应命名为墨菲重排，以纪念R.C.墨菲。墨菲重排从HEA的PFB-TMS衍生物的前体离子m/z 399产生产物离子m/z 253和m/z 89，并中性丢失146 Da。我们提议将在类二十烷酸8-异前列腺素F2α（8-isoPGF）及其2,3-二去甲 - 和2,3-二去甲 -5,6-二氢代谢物、F和E前列腺素的主要尿代谢物（MUM），即分别为PGF-MUM和PGE-MUM中观察到的墨菲型重排，以及药物乙酰水杨酸（阿司匹林）的PFB酯的m/z 179 [M - PFB]的CID也称为墨菲型重排。墨菲重排和墨菲型重排在重排离子以及随后的中性丢失和碎片化方面有所不同。PGF-MUM和PGE-MUM的墨菲型重排包括由于1-或ω-羧酸根阴离子对ω-或1-COO-PFB酯的分子内攻击而导致的198 Da PFBOH的特定中性丢失。通过在NICI模式下对[1,1-O]-和[1,ω-O]-类二十烷酸的PFB-TMS衍生物进行CID研究，可以最好地识别墨菲重排和墨菲型重排。TMSOH（92 Da）和PFBOH（200 Da）（在二羧酸类二十烷酸中）的中性丢失，以及形成m/z 91 [TMSO]的产物离子将表明墨菲重排和墨菲型重排。乙酰水杨酸的PFB酯的m/z 179 [M - PFB]的CID形成m/z 59（乙酸酯）的产物离子将指示墨菲型重排。
