In-depth triacylglycerol profiling using MS3 Q-Trap mass spectrometry

Matias Cabruja; Josefina Priotti; Pablo Domizi; Katharina Papsdorf; Deanna L Kroetz; Anne Brunet; Kévin Contrepois; Michael P Snyder

doi:10.1016/j.aca.2021.339023

In-depth triacylglycerol profiling using MS³ Q-Trap mass spectrometry

Anal Chim Acta. 2021 Nov 1:1184:339023. doi: 10.1016/j.aca.2021.339023. Epub 2021 Sep 3.

Authors

Matias Cabruja¹, Josefina Priotti², Pablo Domizi³, Katharina Papsdorf¹, Deanna L Kroetz², Anne Brunet¹, Kévin Contrepois⁴, Michael P Snyder⁵

Affiliations

¹ Department of Genetics, Stanford University, Stanford, CA, USA.
² Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
³ Department of Pediatrics, Stanford University, Stanford, CA, USA.
⁴ Department of Genetics, Stanford University, Stanford, CA, USA. Electronic address: kcontrep@stanford.edu.
⁵ Department of Genetics, Stanford University, Stanford, CA, USA. Electronic address: mpsnyder@stanford.edu.

Abstract

Total triacylglycerol (TAG) level is a key clinical marker of metabolic and cardiovascular diseases. However, the roles of individual TAGs have not been thoroughly explored in part due to their extreme structural complexity. We present a targeted mass spectrometry-based method combining multiple reaction monitoring (MRM) and multiple stage mass spectrometry (MS³) for the comprehensive qualitative and semiquantitative profiling of TAGs. This method referred as TriP-MS3 - triacylglycerol profiling using MS³ - screens for more than 6,700 TAG species in a fully automated fashion. TriP-MS3 demonstrated excellent reproducibility (median interday CV ∼ 0.15) and linearity (median R² = 0.978) and detected 285 individual TAG species in human plasma. The semiquantitative accuracy of the method was validated by comparison with a state-of-the-art reverse phase liquid chromatography (RPLC)-MS (R² = 0.83), which is the most commonly used approach for TAGs profiling. Finally, we demonstrate the utility and the versatility of the method by characterizing the effects of a fatty acid desaturase inhibitor on TAG profiles in vitro and by profiling TAGs in Caenorhabditis elegans.

Keywords: Fatty acid; Lipids; Mass spectrometry; Triacylglycerols.

MeSH terms

Chromatography, Reverse-Phase*
Humans
Mass Spectrometry
Plasma*
Reproducibility of Results
Triglycerides

Substances

Triglycerides

Abstract

MeSH terms

Substances

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