Mass spectrometric determination of fatty acids

Patent metadata

Field	Value
Publication number	US-11017991-B2
Application number	US-201916359874-A
Country	US
Kind code	B2
Filing date	Mar 20, 2019
Priority date	Jun 22, 2011
Publication date	May 25, 2021
Grant date	May 25, 2021

Abstract

The invention relates to the detection of fatty acids. In a particular aspect, the invention relates to methods for detecting very long chain fatty acids and branched chain fatty acids by mass spectrometry.

First claim

That which is claimed is:

1. A method for determining an amount of one or more underivatized fatty acids in a sample by mass spectrometry, the method comprising:
(a) subjecting the sample containing an amount of one or more underivatized fatty acids to an ionization source to generate one or more underivatized fatty acid ions detectable by mass spectrometry, wherein the one or more underivatized fatty acids is selected from the group consisting of docosanoic acid, tetracosanoic acid, hexacosanoic acid, pristanic acid, and phytanic acid;
(b) determining an amount of the one or more underivatized fatty acid ions by mass spectrometry; and
(c) determining the amount of the one or more underivatized fatty acids in the sample from the amount of the one or more underivatized fatty acid ions determined in step (b).

2. The method of claim 1 , wherein said fatty acid is pristanic acid.

3. The method of claim 1 , wherein said fatty acid is phytanic acid.

4. The method of claim 1 , wherein said fatty acid is docosanoic acid.

5. The method of claim 1 , wherein said fatty acid is tetracosanoic acid.

6. The method of claim 1 , wherein said fatty acid is hexacosanoic acid.

7. The method of claim 1 , wherein the ionization source is electron ionization, chemical ionization, electrospray ionization (ESI), photon ionization, photoionization, atmospheric pressure photoionization (APPI), laser diode thermal desorption (LDTD), fast atom bombardment (FAB), liquid secondary ionization (LSI), matrix assisted laser desorption ionization (MALDI), field ionization, field desorption, thermospray ionization, plasmaspray ionization, surface enhanced laser desorption ionization (SELDI), inductively coupled plasma (ICP), or particle beam ionization.

8. The method of claim 1 , wherein the sample is subjected to liquid/liquid extraction prior to ionization.

9. The method of claim 1 , wherein the one or more fatty acids are subjected to a liquid chromatography column prior to ionization.

10. The method of claim 9 , wherein the liquid chromatography column comprises a high performance liquid chromatography (HPLC), reverse phase liquid chromatography (RPLC), turbulent flow liquid chromatography (TFLC), or high turbulence liquid chromatography (HTLC).

11. The method of claim 1 , wherein the method further comprises determining an amount of one or more internal standards added prior to step (a).

12. The method of claim 11 , wherein the internal standard is pristanic acid- 2 H 3 phytanic acid- 2 H 3 , docosanoic acid- 2 H 3 , tetracosanoic acid- 2 H 3 , or hexacosanoic acid- 2 H 3 .

13. A method of diagnosing or monitoring a peroxisomal disorder comprising determining an amount of one or more fatty acids in a patient sample by steps of claim 1 .

14. The method of claim 13 , wherein an abnormal level of fatty acids is indicative of the peroxisomal disorder.

15. The method of claim 14 , wherein the peroxisomal disorder is Zellweger syndrome, pseudo-Zellweger syndrome, infantile and adult Refsum disease, adrenoleukodystrophy, rhizomelic chondrodysplasia punctata type 1 (RCDP-1), D-bifunctional protein deficiency, or acyl-coA oxidase deficiency.

16. A method for determining an amount of one or more underivatized fatty acids in a sample by mass spectrometry, the method comprising:
(a) subjecting the sample containing an amount of underivatized fatty acids to a hexane extraction, wherein the one or more underivatized fatty acids is selected from the group consisting of docosanoic acid, tetracosanoic acid, hexacosanoic acid, pristanic acid, and phytanic acid;
(b) subjecting the sample to liquid chromatography;
(c) subjecting the sample to an ionization source to generate one or more underivatized fatty acid ions detectable by mass spectrometry;
(d) determining an amount of the one or more underivatized fatty acid ions by mass spectrometry; and
(e) determining the amount of the underivatized fatty acids in the sample from the amount of the one or more underivatized fatty acid ions determined in step (d).

17. The method of claim 16 , wherein said fatty acid is pristanic acid.

18. The method of claim 16 , wherein said fatty acid is phytanic acid.

19. The method of claim 16 , wherein said fatty acid is docosanoic acid.

20. The method of claim 16 , wherein said fatty acid is tetracosanoic acid.

21. The method of claim 16 , wherein said fatty acid is hexacosanoic acid.

22. The method of claim 16 , wherein the ionization source is electron ionization, chemical ionization, electrospray ionization (ESI), photon ionization, photoionization, atmospheric pressure photoionization (APPI), laser diode thermal desorption (LDTD), fast atom bombardment (FAB), liquid secondary ionization (LSI), matrix assisted laser desorption ionization (MALDI), field ionization, field desorption, thermospray ionization, plasmaspray ionization, surface enhanced laser desorption ionization (SELDI), inductively coupled plasma (ICP), or particle beam ionization.

23. The method of claim 16 , wherein said sample is subjected to an acid hydrolysis prior to ionization.

24. The method of claim 16 , wherein the method further comprises determining an amount of one or more internal standards added prior to step (a).

25. The method of claim 24 , wherein the internal standard is pristanic acid- 2 H 3 phytanic acid- 2 H 3 , docosanoic acid- 2 H 3 , tetracosanoic acid- 2 H 3 , or hexacosanoic acid- 2 H 3 .

26. A method of diagnosing or monitoring a peroxisomal disorder comprising determining an amount of one or more fatty acids in a patient sample by steps of claim 16 .

27. The method of claim 26 , wherein an abnormal level of fatty acids is indicative of the peroxisomal disorder.

28. The method of claim 27 , wherein the peroxisomal disorder is Zellweger syndrome, pseudo-Zellweger syndrome, infantile and adult Refsum disease, adrenoleukodystrophy, rhizomelic chondrodysplasia punctata type 1 (RCDP-1), D-bifunctional protein deficiency, or acyl-coA oxidase deficiency.

Assignees

• Quest Diagnostics Invest Inc
• Quest Diagnostics Invest Incoporated

Inventors

• Goldman Scott

Classifications

• G01N33/92 Primary

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

• H01J49/10

  Ion sources; Ion guns · CPC title

• Y10T436/20

  Oxygen containing · CPC title

• Y10T436/200833

  Carbonyl, ether, aldehyde or ketone containing · CPC title

• G01N2560/00

  Chemical aspects of mass spectrometric analysis of biological material · CPC title