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000279434 041__ $$aEnglish
000279434 1001_ $$aWang, Lian Y$$b0
000279434 245__ $$aLabel-free quantitative shotgun analysis of bis(monoacylglycero)phosphate lipids.
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000279434 520__ $$aInterest in the role of bis(monoacylglycero)phosphate (BMP) lipids in lysosomal function has significantly grown in recent years. Emerging evidence highlights BMPs as critical players not only in Niemann-Pick disease type C (NPC) but also in other pathologies such as neurodegeneration, cardiovascular diseases, and cancers. However, the selective analysis of BMPs is significantly hindered by isomeric phosphatidylglycerol (PG) lipids. While this can be addressed by chromatographic separation, it poses a significant challenge for shotgun lipidomics approaches. Here, we present a shotgun lipidomics strategy to detect and separate BMPs from PGs using differential fragmentation of sodiated ions. This approach, including isotope correction, is integrated into an existing quantitative shotgun lipidomics workflow (Lipidyzer combined with Shotgun Lipidomics Assistant software) that simultaneously quantifies >1400 lipids. Validation using K-562 cell extracts demonstrated acceptable linearity, trueness, repeatability, and a limit of quantification of 0.12 µM, confirming robust analytical performance. Finally, characteristic accumulation of BMP lipids is shown in bone marrow-derived macrophages from NPC mice, demonstrating its applicability. Our method presents a quantitative, selective, rapid, and robust solution for shotgun-based BMP analysis without the need for extensive chromatographic separation or derivatization. The integration of BMP lipid detection into the Lipidyzer platform, alongside the recently launched iSODA data visualization tool, empowers chemists and biologists to gain deeper insights into BMP lipid biology.
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000279434 650_7 $$2Other$$aBMP
000279434 650_7 $$2Other$$aFlow injection
000279434 650_7 $$2Other$$aLabel free
000279434 650_7 $$2Other$$aMass spectrometry
000279434 650_7 $$2Other$$aShotgun lipidomics
000279434 650_7 $$2NLM Chemicals$$aMonoglycerides
000279434 650_7 $$2NLM Chemicals$$abis(monoacylglyceryl)phosphate
000279434 650_7 $$2NLM Chemicals$$aLysophospholipids
000279434 650_2 $$2MeSH$$aMonoglycerides: analysis
000279434 650_2 $$2MeSH$$aMonoglycerides: metabolism
000279434 650_2 $$2MeSH$$aAnimals
000279434 650_2 $$2MeSH$$aLipidomics: methods
000279434 650_2 $$2MeSH$$aMice
000279434 650_2 $$2MeSH$$aHumans
000279434 650_2 $$2MeSH$$aLysophospholipids: analysis
000279434 650_2 $$2MeSH$$aLysophospholipids: metabolism
000279434 650_2 $$2MeSH$$aNiemann-Pick Disease, Type C: metabolism
000279434 650_2 $$2MeSH$$aMacrophages: chemistry
000279434 650_2 $$2MeSH$$aMacrophages: metabolism
000279434 650_2 $$2MeSH$$aLimit of Detection
000279434 650_2 $$2MeSH$$aTandem Mass Spectrometry: methods
000279434 7001_ $$aDerks, Rico J E$$b1
000279434 7001_ $$aBrewster, Kevin A J$$b2
000279434 7001_ $$0P:(DE-2719)9002550$$aPrtvar, Danilo$$b3$$udzne
000279434 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b4$$udzne
000279434 7001_ $$0P:(DE-2719)9001700$$aBerghoff, Stefan A$$b5$$udzne
000279434 7001_ $$00000-0003-1684-1894$$aGiera, Martin$$b6
000279434 773__ $$0PERI:(DE-600)1459122-4$$a10.1007/s00216-025-05890-4$$gVol. 417, no. 16, p. 3665 - 3673$$n16$$p3665 - 3673$$tAnalytical and bioanalytical chemistry$$v417$$x1618-2642$$y2025
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