Clinical method for the genetic screening of newborns using tandem mass spectrometry and internal standards therefor

• US 20060008922A1
• Filed: 06/28/2005
• Published: 01/12/2006
• Est. Priority Date: 01/30/1999
• Status: Active Grant

• Current Assignee: PerkinElmer Genetics, Inc. (Revvity, Inc.)
• Original Assignee: PerkinElmer Genetics, Inc. (Revvity, Inc.)
• Inventors: Chace, Donald H.
• Granted Patent: US 7,297,545 B2
• Time in Patent Office: Days
• US Class Current: 436/518
• CPC Class Codes: G01N 2800/02 Nutritional disorders
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: H01J 49/0036 Step by step routines describing the handling of the data generated during a measurement
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

A method for screening newborns using electrospray tandem mass spectrometry. The method improves the current protocols that use tandem mass spectrometry by assuring accurate and consistent results at the clinical level through enhanced quality controls and quality assurance protocols as applied to the scan profiling and sample preparation of blood spots from newborns. Specific additives are used in precise concentrations of internal standards, employing detailed controls adapted to distinguish twenty metabolites, which are scanned and vigorously compared to known spectra results. Revealing peaks, metabolite concentration, and scan intensities in the quality assurance steps are then compared to a range of thresholds to determine whether or not the sample is contaminated, drug-ridden, diagnosable, or unacceptable. All spectra results and quality assurance flags are organized in spreadsheet form and exported to a database where values are compiled and stored for daily output results and trend analysis. The method provides for high-throughput and quality results, having a consistent predictability for genetically testing newborns efficiently and accurately.

Claims

1-16. -16. (canceled)

17. An internal standard preparation comprising ²H₉-carnitine, ²H₃-acetylcarnitine, ²H₃-propionylcarnitine, ²H₃-butyrylcarnitine, ²H₉-isovalerylcarnitine, ²H₃-octanoylcarnitine, ²H₉-myristoylcarnitine, and ²H₃-palmitoylcarnitine.

18. The internal standard preparation of claim 17, wherein said preparation is a methonalic solution.

19. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²H₉-carnitine is present at a concentration of about 0.76 nmol/l.

20. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²H₃-acetylcarnitine is present at a concentration of about 0.19 nmol/l.

21. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²H₃-propionylcarnitine is present at a concentration of about 0.04 nmol/l.

22. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²H₃-butyrylcarnitine is present at a concentration of about 0.04 nmol/l.

23. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²H₉-isovalerylcarnitine is present at a concentration of about 0.04 nmol/l.

24. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²H₃-octanoylcarnitine is present at a concentration of about 0.04 nmol/l.

25. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²Hg-myristoylcarnitine is present at a concentration of about 0.04 nmol/l.

26. The internal standard preparation of claim 17, wherein said preparation is a solution and said ²H₃-palmitoylcarnitine is present at a concentration of about 0.08 nmol/1.

27. The internal standard preparation of claim 17, wherein at least two of said ²H₉-propionylcarnitine, ²H₃-butyrylcarnitine, ²H₉-isovalerylcarnitine, ²H₃-octanoylcarnitine, and ²H₉-myristoylcarnitine are present in about equal amounts.

28. The internal standard preparation of claim 17, wherein the preparation includes an amount of ²H₃-palmitoylcarnitine that is about double that of at least one of ²H₃-propionylcarnitine, ²H₃-butyrylcarnitine, ²H₉-isovalerylcarnitine, ²H₃-octanoylcarnitine, and ²H₉-myristoylcarnitine.