Method for analysis of compounds with amino group and analytical reagent therefor

Patent metadata

Field	Value
Publication number	US-9658234-B2
Application number	US-201615003235-A
Country	US
Kind code	B2
Filing date	Jan 21, 2016
Priority date	Feb 14, 2002
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

The present invention provides a method for the analysis of a compound with amino group (e.g., an amino acid or peptide) contained in a sample and convenient manner with a high sensitivity. The compound with amino group in a sample containing the compound with amino group is labeled with a specific carbamate compound such as p-trimethylammonium anilyl-N-hydroxysuccinimidyl carbamate iodide to enhance the selectivity and sensitivity. The present invention is preferably used in conjunction with mass spectrometry such as MS/MS method to facilitate quantitative analysis. The present invention further provides labeling reagents for mass spectrometry.

First claim

The invention claimed is:

1. A carbamate compound represented by formula (1):

wherein Ar is an aromatic carbocyclic group or an aromatic heterocyclic group residue, wherein said aromatic carbocyclic group or said aromatic heterocyclic group residue has a substituent, and
wherein, in the bond between Ar and the nitrogen atom of the carbamate group, a carbon atom within the ring of Ar is bound to the nitrogen atom of the carbamate group, whereby said carbamate compound may be in a form of a salt, and
wherein said substituent contains a sulfonic acid group, a phosphoric acid group, a guanidyl group, a dialkylamino group or a trialkyl ammonium group.

2. A carbamate compound according to claim 1 , wherein said substituent contains a dialkylamino group or a trialkyl ammonium group.

3. A carbamate compound according to claim 1 , wherein the alkyl groups in said dialkylamino group and said trialkylammonium group are each independently an alkyl group having 1 to 5 carbon atoms.

4. A carbamate compound according to claim 1 , wherein Ar is a phenyl group.

5. A carbamate compound according to claim 1 , wherein Ar is a quinolyl group.

6. A method for analyzing a compound with an amino group in a sample, containing at least a compound with an amino group by means of mass spectrometry, said method comprising
labeling said compound with an amino group in said sample by reacting said compound with an amino group with a carbamate compound according to claim 1 , to obtain a mixture comprising a labeled compound; and
subjecting said labeled compound to mass spectrometry.

7. A method according to claim 6 , comprising subjecting said labeled compound to tandem mass spectrometry.

8. A method according to claim 7 , wherein said tandem mass spectrometry is selected from the group consisting of a selected reaction monitoring method, a precursor ion scan method, and a constant neutral loss scan method.

9. A method according to claim 6 , wherein said compound with an amino group is at least one type of compound selected from the group consisting of an amine, an amino acid, a peptide, and a protein.

10. A method according to claim 6 , wherein said compound with an amino group is a primary amine or a secondary amine.

11. A method according to claim 6 , wherein said labeled compound is separated from said mixture before being subjected to mass spectrometry.

12. A method according to claim 11 , wherein said labeled compound is separated from said mixture by liquid chromatography.

13. A method according to claim 11 , wherein said labeled compound is separated from said mixture by reversed phase column.

14. A method according to claim 6 , wherein the amount of said carbamate compound is 10- to 1000-fold mole equivalents to said compound with an amino group.

15. A method for labelling a compound with an amino group in a sample containing at least a compound with an amino group, which method is suitable for mass spectrometry, comprising
reacting said compound with an amino group in sample with a carbamate compound according to claim 1 .

Assignees

• Ajinomoto Kk

Inventors

• Miyano Hiroshi
• Yahashi Akihisa
• Shimbo Kazutaka
• Nakazawa Masakazu
• Hirayama Kazuo

Classifications

• Y10T436/24

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

• Y10T436/145555

  Hetero-N · CPC title

• Y10T436/14

  Heterocyclic carbon compound [i.e. , O, S, N, Se, Te, as only ring hetero atom] · CPC title

• Y10T436/13

  Tracers or tags · CPC title

• G01N2458/15

  Non-radioactive isotope labels, e.g. for detection by mass spectrometry · CPC title