Liquid chromatography coordination ion-spray mass spectrometry (LC?CIS?MS) of docosahexaenoate ester hydroperoxides

Seal, Jennifer; Porter, Ned A.

doi:10.1007/s00216-003-2274-6

Cited by 25 publications

(19 citation statements)

References 18 publications

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“…For this reason, there have been few reports describing the analysis of HpDoHE and HDoHE by LC-MS/MS [6,35-38]. To the best of our knowledge, this study is the first analytical report describing the detailed MS/MS characterization and the development of an SRM method for reliably discriminating all twelve positional isomers of both HpDoHE and HDoHE.…”

Section: Resultsmentioning

confidence: 98%

The Development of a Specific and Sensitive LC-MS-Based Method for the Detection and Quantification of Hydroperoxy- and Hydroxydocosahexaenoic Acids as a Tool for Lipidomic Analysis

et al. 2013

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Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid that is highly enriched in the brain, and the oxidation products of DHA are present or increased during neurodegenerative disease progression. The characterization of the oxidation products of DHA is critical to understanding the roles that these products play in the development of such diseases. In this study, we developed a sensitive and specific analytical tool for the detection and quantification of twelve major DHA hydroperoxide (HpDoHE) and hydroxide (HDoHE) isomers (isomers at positions 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19 and 20) in biological systems. In this study, HpDoHE were synthesized by photooxidation, and the corresponding hydroxides were obtained by reduction with NaBH4. The isolated isomers were characterized by LC-MS/MS, and unique and specific fragment ions were chosen to construct a selected reaction monitoring (SRM) method for the targeted quantitative analysis of each HpDoHE and HDoHE isomer. The detection limits for the LC-MS/MS-SRM assay were 1−670 pg for HpDoHE and 0.5−8.5 pg for HDoHE injected onto a column. Using this method, it was possible to detect the basal levels of HDoHE isomers in both rat plasma and brain samples. Therefore, the developed LC-MS/MS-SRM can be used as an important tool to identify and quantify the hydro(pero)xy derivatives of DHA in biological system and may be helpful for the oxidative lipidomic studies.

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Section: Resultsmentioning

confidence: 98%

The Development of a Specific and Sensitive LC-MS-Based Method for the Detection and Quantification of Hydroperoxy- and Hydroxydocosahexaenoic Acids as a Tool for Lipidomic Analysis

et al. 2013

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“…3. Recently, characterization of 10 hydroperoxides from oxidation of docosahexaenoic acid (DHA) has also been accomplished by the same technique (78).…”

Section: Lipid Autoxidation and Free Radical Mechanisms 175mentioning

confidence: 99%

New Insights Regarding the Autoxidation of Polyunsaturated Fatty Acids

Yin

Porter

2005

Antioxidants & Redox Signaling

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166

106

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Free radical-initiated autoxidation of polyunsaturated fatty acids (PUFAs) has been implicated in numerous human diseases, including atherosclerosis and cancer. This review covers the free radical mechanisms of lipid oxidation and recent developments of analytical techniques to analyze the lipid oxidation products. Autoxidation of PUFAs generates hydroperoxides as primary oxidation products, and further oxidation leads to cyclic peroxides as secondary oxidation products. Characterization of these oxidation products is accomplished by several mass spectrometric techniques. Ag+ coordination ion spray mass spectrometry has proven to be a powerful tool to analyze the intact lipid peroxides. Monocyclic peroxides, bicyclic endoperoxides, serial cyclic peroxides, and a novel class of endoperoxides (dioxolane-isoprostane peroxides) have been identified from the oxidation of arachidonate. Electron capture atmospheric pressure chemical ionization mass spectrometry has been applied to study lipid oxidation products after derivatization. All eight possible diastereomeric isoprostanes are observed from the oxidation of a single hydroperoxide precursor. 5- and 15-series isoprostanes are more abundant than the 8- and 12-series because the precursors that lead to 8- and 12-series compounds can undergo further oxidation and form dioxolane-isoprostane peroxides. Furthermore, formation of isoprostanes from 15-hydroperoxyeicosatetraenoate occurs from beta-fragmentation of the corresponding peroxyl radical to generate a pentadienyl radical rather than a "dioxetane" intermediate, as previously suggested.

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“…The reaction was stirred under oxygen at 37°C for 24 h. The reaction was quenched by adding 2 mg of butylated hydroxytoluene, and N-methyl benzohydroxamic acid was removed by flash chromatography on silica gel. The hydroperoxides were analyzed and separated by analytical and semipreparative HPLC, and reasonable separation was obtained as described previously (24). The separated fractions of primary hydroperoxides were converted to more highly oxidized peroxides according to SCHEME 2 our previous procedure (18).…”

Section: Methodsmentioning

confidence: 99%

“…To verify the predicted fragmentation of each regioisomeric F 4 -NP, we adopted the strategy of generating specific NP regioisomers from parent hydroperoxides. Fortunately, most of these 10 precursor hydroperoxides of DHA methyl esters (HpDHA) can be well separated by normal phase HPLC as we have described previously (24). Thus, a mixture of DHA hydroperoxides was generated by a free radical reaction using a good hydrogen atom donor N-methyl benzohydroxamic acid.…”

Section: Regioselectivity Of Neuroprostanes Formed From the Autoxidatmentioning

confidence: 99%

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Regiochemistry of Neuroprostanes Generated from the Peroxidation of Docosahexaenoic Acid in Vitro and in Vivo

Yin¹,

Musiek²,

Gao³

et al. 2005

Journal of Biological Chemistry

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Isoprostanes (IsoPs) are isomers of prostaglandins that are generated from the free radical-initiated peroxidation of arachidonic acid (C20.4 -6). IsoPs exert potent bioactivity and are regarded as the "gold standard" to assess oxidative stress in various human diseases. Analogously, autoxidation of docosahexaenoic acid (DHA, C22.6 -3) generates an array of IsoP-like compounds that are termed neuroprostanes (NPs). A major class of NPs identified in vitro and in vivo contains F-type prostane rings and are know as F 4 -NPs. A number of different F 4 -NP regioisomers are formed from the peroxidation of DHA. Among the eight possible regioisomeric groups, we hypothesize that 4-and 20-series NPs are generated in greater amounts than other classes because the precursors that lead to regioisomers other than those of the 4-and 20-series can be further oxidized to form novel dioxolane-IsoP-like compounds, analogous to those generated from arachidonate. Various mass spectrometric approaches, including electron capture atmospheric pressure chemical ionization mass spectrometry, were utilized to analyze NPs formed in vitro and in vivo based on their characteristic fragmentation in the gas phase. Experimental results were consistent with our hypothesis that 4-and 20-series NP regioisomers are preferentially generated. The discovery of regioselectivity in the formation of NPs will allow studies of the biological activities of NPs to focus on the more abundantly generated compounds to determine their role in modulating the pathophysiological consequences of DHA oxidation and oxidant stress.

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Liquid chromatography coordination ion-spray mass spectrometry (LC?CIS?MS) of docosahexaenoate ester hydroperoxides

Cited by 25 publications

References 18 publications

The Development of a Specific and Sensitive LC-MS-Based Method for the Detection and Quantification of Hydroperoxy- and Hydroxydocosahexaenoic Acids as a Tool for Lipidomic Analysis

The Development of a Specific and Sensitive LC-MS-Based Method for the Detection and Quantification of Hydroperoxy- and Hydroxydocosahexaenoic Acids as a Tool for Lipidomic Analysis

New Insights Regarding the Autoxidation of Polyunsaturated Fatty Acids

Regiochemistry of Neuroprostanes Generated from the Peroxidation of Docosahexaenoic Acid in Vitro and in Vivo

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