Methods for analysis of isomeric lipids

Patent metadata

Field	Value
Publication number	US-9360455-B2
Application number	US-201314655263-A
Country	US
Kind code	B2
Filing date	Dec 13, 2013
Priority date	Dec 26, 2012
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

Abstract

A method for analyzing a sample that contains a plurality of lipid isomers is described that involves forming one or more lipid metal ion adducts and transporting the one or more lipid metal ion adducts through a differential mobility spectrometer to cause separation of the one or more lipid metal ion adducts from each other. The lipid isomers can be chosen, for example, from fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipids, and prenol lipids. Particular examples include phosphatidylcholine regioisomers such as 1-palmatoyl-2-oleoyl-sn-phosphatidylcholine (POPC) and 1-oleoyl-2-palmatoyl-sn-phosphatidylcholine and triacylglycerols containing palmetic and oleic acid groups. The metal chosen can include a cationization reagent that contains sodium, potassium, silver or lithium.

First claim

The invention claimed is:

1. A method for analyzing a sample, comprising:
a. ionizing a sample containing or suspected of containing a plurality of lipid isomers so as to form one or more lipid silver adducts, at least one of the plurality of lipid isomers being selected from the group consisting of fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipids, and prenol lipids, and wherein an acyl chain of the at least one of the plurality of lipid isomers comprises at least one unsaturated carbon-carbon double bond; and
b. transporting said one or more lipid silver adducts through a differential mobility spectrometer to effect separation of said one or more lipid silver adducts;
wherein ionizing the sample comprises reacting the sample with a salt of silver.

2. The method of claim 1 , wherein the plurality of lipid isomers comprises 1 oleoyl-2-palmatoyl-sn-phosphatidylcholine and 1-palmatoyl-2-oleoyl-sn-phosphatidylcholine.

3. The method of claim 1 , further comprising determining a relative abundance of the plurality of lipid isomers in the sample.

4. The method of claim 1 , further comprising increasing a throttle gas flow rate to increase a drift time or a residence time of the lipid silver adducts in the differential mobility spectrometer.

5. The method of claim 1 , wherein the sample is not passed through a liquid chromatography column prior to being transmitted through the differential mobility spectrometer.

6. The method of claim 1 , wherein the differential mobility spectrometer comprises a high-field asymmetric waveform ion mobility spectrometry device.

7. The method of claim 1 , further comprising:
c. enhancing the separation of the lipid silver adducts by the addition of a chemical modifier to the differential mobility spectrometer.

8. The method of claim 7 , wherein the chemical modifier used in the differential mobility spectrometer is selected from the group consisting of alcohols, aldehydes, amides, amines, aromatics, esters, ethers, halocarbons, ketones, nitriles, thiols, or water.

9. The method of claim 7 , wherein the plurality of lipid isomers comprises isomeric triacylglycerol molecules.

10. The method of claim 9 wherein the isomeric triacylglycerol molecules comprise two palmetic acid groups and one oleic acid group.

11. The method of claim 9 wherein the chemical modifier is propanol.

12. A method of mass spectrometry, comprising:
a. exposing a sample comprising a plurality of isomeric lipids to a cationization reagent so as to stabilize a configuration of said plurality of isomeric lipids, at least one of the plurality of isomeric lipids being selected from the group consisting of fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipids, and prenol lipids, and wherein an acyl chain of the at least one of the plurality of isomeric lipids comprises at least one unsaturated carbon-carbon double bond and wherein said cationization reagent comprises a silver salt;
b. transporting said stabilized isomeric lipids through an ion mobility spectrometer so as to effect separation of said plurality of one or more stabilized isomeric lipids;
c. transporting the separated plurality of one or more stabilized isomeric lipids to a mass spectrometer for analysis.

13. A method for analyzing a sample containing or suspected of containing a plurality of isomeric lipids, at least one of the plurality of isomeric lipids being selected from the group consisting of fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipids, and prenol lipids, and wherein an acyl chain of the at least one of the plurality of isomeric lipids comprises at least one unsaturated carbon-carbon double bond, the method comprising:
a. forming one or more silver adducts with said isomeric lipids; and
b. transporting said one or more silver adducts through a differential mobility spectrometer to effect separation of said one or more silver adducts.

Assignees

• Dh Technologies Dev Pte Ltd

Inventors

• Campbell John L
• Leblanc Yves

Classifications

• G01N33/92

  involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} · CPC title

• H01J49/0031

  Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence) · CPC title

• G01N27/622 Primary

  Ion mobility spectrometry · CPC title

• Y10T436/24

  Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry · CPC title

• G01N27/624 Primary

  Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS] · CPC title