TY  - JOUR
AU  - Wang, Lian Y
AU  - Derks, Rico J E
AU  - Brewster, Kevin A J
AU  - Prtvar, Danilo
AU  - Tahirovic, Sabina
AU  - Berghoff, Stefan A
AU  - Giera, Martin
TI  - Label-free quantitative shotgun analysis of bis(monoacylglycero)phosphate lipids.
JO  - Analytical and bioanalytical chemistry
VL  - 417
IS  - 16
SN  - 1618-2642
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2025-00765
SP  - 3665 - 3673
PY  - 2025
AB  - Interest 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.
KW  - Monoglycerides: analysis
KW  - Monoglycerides: metabolism
KW  - Animals
KW  - Lipidomics: methods
KW  - Mice
KW  - Humans
KW  - Lysophospholipids: analysis
KW  - Lysophospholipids: metabolism
KW  - Niemann-Pick Disease, Type C: metabolism
KW  - Macrophages: chemistry
KW  - Macrophages: metabolism
KW  - Limit of Detection
KW  - Tandem Mass Spectrometry: methods
KW  - BMP (Other)
KW  - Flow injection (Other)
KW  - Label free (Other)
KW  - Mass spectrometry (Other)
KW  - Shotgun lipidomics (Other)
KW  - Monoglycerides (NLM Chemicals)
KW  - bis(monoacylglyceryl)phosphate (NLM Chemicals)
KW  - Lysophospholipids (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40343460
C2  - pmc:PMC12206189
DO  - DOI:10.1007/s00216-025-05890-4
UR  - https://pub.dzne.de/record/279434
ER  -