IP Library Granted Patent US 11,181,530
Granted Patent B2
US 11,181,530 · App. 16/305,078 · Granted Nov 23, 2021

Mass spectrometry method for detection and quantitation of metabolites

Inventors: Lisa Ford (Durham, NC); Qibo Zhang (Cary, NC); Klaus Peter Adam (Cary, NC)
Assignee: Metabolon, Inc.
G01N33/6812G01N30/7233G01N2560/00
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Quick Facts
Patent No.
US 11,181,530
App. No.
16/305,078
Granted
Nov 23, 2021
Kind
B2
Abstract

A method for determining the amount of one or more analytes in a sample by mass spectrometry is described. The one or more analytes are selected from the group consisting of alpha-hydroxybutyrate (2-HB), linoleoyl LPC (LGPC), oleic acid, 3-hydroxybutyrate (3-HB), 4-methyl-2-oxopentanoate (4-MOP), pantothenate, and serine. The method includes a) subjecting the sample to an ionization source under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the one or more of the analytes, wherein the analytes are not derivatized prior to ionization; b) measuring, by tandem mass spectrometry, the amount of the one or more ions from each of the one or more analytes; and c) using the measured amount of the one or more ions to determine the amount of each of the one or more analytes in the sample.

Claims (20)

1. A method for determining in a sample, by mass spectrometry, the amount of two or more analytes selected from the group consisting of alpha-hydroxybutyrate (2-HB), linoleoyl LPC (LGPC), oleic acid, 3-hydroxybutyrate (3-HB), 4-methyl-2-oxopentanoate (4-MOP), pantothenate, and serine, the method comprising:

a) purifying a single injection of the sample by liquid chromatography;

b) subjecting the single injection of the sample to an ionization source under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the two or more analytes, wherein the analytes are not derivatized prior to ionization;

c) measuring, by mass spectrometry, the amount of the two or more ions from each of the two or more analytes in the single injection of the sample, wherein the mass spectrometer is operated in negative mode; and

d) using the measured amount of the two or more ions to determine the amount of each of the two or more analytes in the single injection of the sample;

wherein at least one of the two or more analytes is selected from the group consisting of 2-HB, LGPC, 3-HB, 4-MOP, and oleic acid and a second of the two or more analytes is selected from the group consisting of serine and pantothenate.

2. The method of claim 1 , wherein the two or more analytes comprise 2-HB and pantothenate.

3. The method of claim 1 , wherein the two or more analytes comprise 2-HB and serine.

4. The method of claim 1 , wherein the two or more analytes comprise LGPC and pantothenate.

5. The method of claim 1 , wherein the two or more analytes comprise LGPC and serine.

6. The method of claim 1 , wherein the amount 2-HB, LGPC, oleic acid, 3-HB, 4-MOP, pantothenate, and serine is determined.

7. The method of claim 1 , wherein said liquid chromatography is selected from the group consisting of high performance liquid chromatography, ultra high performance liquid chromatography, and turbulent flow liquid chromatography.

8. The method of claim 1 , wherein an internal standard is used to determine the amount of the two or more analytes in the sample.

9. The method of claim 8 , wherein the internal standard comprises an isotopically labeled analogue of at least one of the two or more analytes to be measured.

10. The method of claim 1 , wherein the sample comprises a biological sample.

11. The method of claim 10 , wherein the sample is selected from the group consisting of blood, plasma and serum.

12. The method of claim 1 , wherein at least one of the two or more analytes is selected from the group consisting of 2-HB and LGPC and a second of the two or more analytes is selected from the group consisting of serine and pantothenate.

13. The method of claim 12 , wherein one of the two or more analytes is 2-HB and a second of the two or more analytes is selected from the group consisting of pantothenate, and serine.

14. The method of claim 12 , wherein one of the two or more analytes is LGPC and a second of the two or more analytes is selected from the group consisting of pantothenate and serine.

15. The method of claim 1 , wherein a run time for the method is less than 3 minutes.

Assignments (4)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNOR'S NAME FROM " PERCEPTIVE CREDIT HOLDINGS ILL, LP" TO "PERCEPTIVE CREDIT HOLDINGS III, LP" PREVIOUSLY RECORDED AT REEL: 66971 FRAME: 0054. ASSIGNOR(S) HEREBY CONFIRMS THE RELEASE OF SECURITY INTEREST. Recorded Apr 4, 2024
From: PERCEPTIVE CREDIT HOLDINGS III, LP
To: METABOLON, INC.
Reel/Frame 067019/0662 →
RELEASE OF SECURITY INTEREST Recorded Apr 1, 2024
From: PERCEPTIVE CREDIT HOLDINGS ILL, LP
To: METABOLON, INC.
Reel/Frame 066971/0054 →
SECURITY AGREEMENT Recorded Jul 24, 2020
From: METABOLON, INC.
To: PERCEPTIVE CREDIT HOLDINGS III, LP
Reel/Frame 053313/0406 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 6, 2018
From: FORD, LISA; ZHANG, QIBO; ADAM, KLAUS PETER
To: METABOLON, INC.
Reel/Frame 048788/0484 →