Mass spectrometry assay for congenital adrenal hyperplasia

Patent metadata

Field	Value
Publication number	US-9921231-B2
Application number	US-201715401797-A
Country	US
Kind code	B2
Filing date	Jan 9, 2017
Priority date	Dec 24, 2008
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

Methods are provided for detecting the amount of one or more CAH panel analytes (i.e., pregnenolone, 17-OH pregnenolone, progesterone, 17-OH progesterone, dehydroepiandrosterone (DHEA), androstenedione, testosterone, deoxycorticosterone, 11-deoxycortisol, and cortisol) in a sample by mass spectrometry. The methods generally involve ionizing one or more CAH panel analytes in a sample and quantifying the generated ions to determine the amount of one or more CAH panel analytes in the sample. In methods where amounts of multiple CAH panel analytes are detected, the amounts of multiple analytes are detected in the same sample injection.

First claim

That which is claimed is:

1. A method for determining the amount of a panel of analytes in a sample by mass spectrometry, the method comprising:
(i) purifying the sample by liquid chromatography;
(ii) ionizing the sample under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the analytes comprising 17-OH progesterone, cortisol, and androstenedione;
(iii) determining by tandem mass spectrometry the amount of the one or more ions from each of the analytes; and
(iv) using the determined amount of the one or more ions to determine the amount of each of the analytes in the sample.

2. The method of claim 1 , wherein said liquid chromatography is high performance liquid chromatography, ultra high performance liquid chromatography, or turbulent flow liquid chromatography.

3. The method of claim 1 , wherein the sample has been purified by solid phase extraction prior to ionization.

4. The method of claim 1 , wherein an internal standard is used for determination of the amount of the analytes in the sample.

5. The method of claim 4 , wherein the internal standard comprises an isotopically labeled analog of at least one of the analytes.

6. The method of claim 1 , wherein the sample comprises plasma or serum.

7. The method of claim 1 , wherein the ionizing comprises ionization by electrospray ionization (ESI).

8. A method for determining the amount of a panel of analytes in a sample by mass spectrometry, the method comprising:
(i) purifying the sample by liquid chromatography;
(ii) ionizing the sample under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the analytes comprising 17-OH progesterone, 17-OH pregnenolone, dehydroepiandrosterone (DHEA), and androstenedione;
(iii) determining by tandem mass spectrometry the amount of the one or more ions from each of the analytes; and
(iv) using the determined amount of the one or more ions to determine the amount of each of the analytes in the sample.

9. The method of claim 8 , wherein said liquid chromatography is high performance liquid chromatography, ultra high performance liquid chromatography, or turbulent flow liquid chromatography.

10. The method of claim 8 , wherein an internal standard is used for determination of the amount of the analytes in the sample.

11. The method of claim 10 , wherein the internal standard comprises an isotopically labeled analog of at least one of the analytes.

12. The method of claim 8 , wherein the sample comprises plasma or serum.

13. A method for determining the amount of a panel of analytes in a sample by mass spectrometry, the method comprising:
(i) purifying the sample by liquid chromatography;
(ii) ionizing the sample under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the analytes comprising 17-OH progesterone, testosterone, and androstenedione;
(iii) determining by tandem mass spectrometry the amount of the one or more ions from each of the analytes; and
(iv) using the determined amount of the one or more ions to determine the amount of each of the analytes in the sample.

14. The method of claim 13 , wherein said liquid chromatography is high performance liquid chromatography, ultra high performance liquid chromatography, or turbulent flow liquid chromatography.

15. The method of claim 13 , wherein an internal standard is used for determination of the amount of the analytes in the sample.

16. The method of claim 15 , wherein the internal standard comprises an isotopically labeled analog of at least one of the analytes.

17. The method of claim 13 , wherein the sample comprises plasma or serum.

18. A method for determining the amount of a panel of analytes in a sample by mass spectrometry, the method comprising:
(i) purifying the sample by liquid chromatography;
(ii) ionizing the sample under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the analytes comprising 17-OH progesterone, testosterone, cortisol, dehydroepiandrosterone (DHEA), and androstenedione;
(iii) determining by tandem mass spectrometry the amount of the one or more ions from each of the analytes; and
(iv) using the determined amount of the one or more ions to determine the amount of each of the analytes in the sample.

19. The method of claim 18 , wherein said liquid chromatography is high performance liquid chromatography, ultra high performance liquid chromatography, or turbulent flow liquid chromatography.

20. The method of claim 18 , wherein an internal standard is used for determination of the amount of the analytes in the sample.

21. The method of claim 20 , wherein the internal standard comprises an isotopically labeled analog of at least one of the analytes.

22. The method of claim 18 , wherein the sample comprises plasma or serum.

23. A method for determining the amount of a panel of analytes in a sample by mass spectrometry, the method comprising:
(i) purifying the sample by liquid chromatography;
(ii) ionizing the sample under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the analytes comprising 17-OH progesterone, testosterone, cortisol, deoxycorticosterone, 11-deoxycortisol, 17-OH pregnenolone, dehydroepiandrosterone (DHEA), progesterone, and androstenedione;
(iii) determining by tandem mass spectrometry the amount of the one or more ions from each of the analytes; and
(iv) using the determined amount of the one or more ions to determine the amount of each of the analytes in the sample.

24. The method of claim 23 , wherein said liquid chromatography is high performance liquid chromatography, ultra high performance liquid chromatography, or turbulent flow liquid chromatography.

25. The method of claim 23 , wherein an internal standard is used for determination of the amount of the analytes in the sample.

26. The method of claim 25 , wherein the internal standard comprises an isotopically labeled analog of at least one of the analytes.

27. The method of claim 23 , wherein the sample comprises plasma or serum.

Assignees

• Quest Diagnostics Invest Inc

Inventors

• Ghoshal Amit
• Clarke Nigel J
• Goldman Mildred M

Classifications

• G01N30/7233

  interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04) · CPC title

• H01J49/0031

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

• G01N2800/04

  Endocrine or metabolic disorders · CPC title

• G01N33/6851

  Methods of protein analysis involving laser desorption ionisation mass spectrometry · CPC title

• G01N33/743 Primary

  Steroid hormones · CPC title