Standard solution for use in analysis of amino acid in plasma

Patent metadata

Field	Value
Publication number	US-9638706-B2
Application number	US-201214232073-A
Country	US
Kind code	B2
Filing date	Jul 19, 2012
Priority date	Jul 21, 2011
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

An external standard solution for use in the analysis of amino acid in plasma, containing,
(1) at least one amino acid selected from the following components A, at a concentration of 0.0007 M to 0.49 M, and (2) (i) at least one amino acid selected from the following components B, at a concentration of 0.2 to 0.9 times of the lowest-concentration amino acid among the amino acids selected from components A, (ii) at least one amino acid selected from the following components C, at a concentration of 0.1 to 0.4 times of the lowest-concentration amino acid among amino acids selected from the components A, or (iii) at least one amino acid selected from the following components D, at a concentration of 0.05 to 0.2 times of the lowest-concentration amino acid among amino acids selected from the components A;
[Components A] valine, glycine, alanine and glutamine [Components B] serine, proline, threonine, taurine, leucine, isoleucine, lysine, histidine, phenylalanine and tyrosine [Components C] asparagine, ornithine, arginine and tryptophan [Components D] glutamic acid, methionine, citrulline and cystine.

First claim

What is claimed is:

1. An external standard solution comprising:
(1) water or buffer,
(2) at least one amino acid selected from the following Components A, at a concentration of 0.0007 M to 0.49 M per amino acid; and
(3) at least one of (i), (ii), or (iii):
(i) at least one amino acid selected from the following Components B, wherein each amino acid selected from Components B has a concentration of 0.2 to 0.9 times that of the lowest-concentration amino acid among amino acids selected from Components A,
(ii) at least one amino acid selected from the following Components C, wherein each amino acid selected from Components C has a concentration of 0.1 to 0.4 times that of the lowest-concentration amino acid among amino acids selected from Components A, and when the external standard solution includes an amino acid selected from Components B, has a concentration of less than 1 times that of the lowest-concentration amino acid among amino acids selected from Components B, or
(iii) at least one amino acid selected from the following Components D, wherein each amino acid selected from Components D has a concentration of 0.05 to 0.2 times that of the lowest-concentration amino acid among amino acids selected from Components A, and when the external standard solution includes an amino acid selected from Components B, has a concentration of less than 1 times that of the lowest-concentration amino acid among amino acids selected from Components B, and when the external standard solution includes Components C, has a concentration of less than 1 times that of the lowest-concentration amino acid among amino acids selected from Components C;

wherein the Components A are valine, glycine, alanine, and glutamine;
wherein the Components B are serine, proline, threonine, taurine, leucine, isoleucine, lysine, histidine, phenylalanine, and tyrosine;
wherein the Components C are asparagine, ornithine, arginine, and tryptophan; and
wherein the Components D are glutamic acid, methionine, citrulline, and cystine.

2. The external standard solution according to claim 1 , wherein the external standard solution contains (1) at least one amino acid selected from Components A, at 0.0007 M to 0.49 M per amino acid, and (2) at least one amino acid selected from Components B, wherein each amino acid selected from Components B has a concentration of 0.2 to 0.9 times that of the lowest-concentration amino acid among amino acids selected from Components A.

3. The external standard solution according to claim 2 , wherein the external standard solution further contains at least one amino acid selected from Components C, wherein each amino acid selected from Components C has a concentration of 0.1 to 0.4 times that of the lowest-concentration amino acid among amino acids selected from Components A, and a concentration of less than 1 times that of the lowest-concentration amino acid among amino acids selected from Components B.

4. The external standard solution according to claim 3 , wherein the external standard solution further contains at least one amino acid selected from Components D, wherein each amino acid selected from Components D has a concentration of 0.05 to 0.2 times that of the lowest-concentration amino acid among amino acids selected from Components A, has a concentration of less than 1 times that of the lowest-concentration amino acid among amino acids selected from Components B, and has a concentration of less than 1 times that of the lowest-concentration amino acid among amino acids selected from the Components C.

5. An external standard substance obtained by lyophilizing the external standard solution according to claim 1 .

6. A method for analyzing amino acids in plasma, the method comprising (i) preparing an external standard solution according to claim 1 ; (ii) analyzing the amino acids in a plasma sample by separation analysis; (iii) preparing a calibration curve with the external standard solution using said separation analysis; and (iv) determining the concentration of amino acids in the plasma sample by applying the calibration curve to the results obtained by the separation analysis of the plasma sample.

7. The method of claim 6 , wherein the separation analysis is conducted by liquid chromatography-mass spectrometry.

8. An external standard solution, comprising water or buffer and valine and at least one of leucine, isoleucine, phenylalanine, tyrosine, histidine, tryptophan, and citrulline;
wherein valine has a concentration of 0.0003 M to 0.49 M;
wherein if leucine is included in the external standard solution, its concentration is 0.1 to less than 1.0 times the concentration of valine;
wherein if isoleucine is included in the external standard solution, its concentration is 0.05 to 0.7 times the concentration of valine;
wherein if phenylalanine is included in the external standard solution, its concentration is 0.1 to 0.6 times the concentration of valine;
wherein if tyrosine is included in the external standard solution, its concentration is 0.1 to 0.7 times the concentration of valine;
wherein if histidine is included in the external standard solution, its concentration is 0.1 to 0.8 times the concentration of valine;
wherein if tryptophan is included in the external standard solution, its concentration is 0.1 to 0.6 times the concentration of valine, and when leucine, isoleucine, phenylalanine, tyrosine, or histidine is included, the concentration of tryptophan is less than 1 times that of the lowest-concentration amino acid of leucine, isoleucine, phenylalanine, tyrosine, or histidine; and
wherein if citrulline is included in the external standard solution, its concentration is 0.01 to 0.3 times the concentration of valine, and when leucine, isoleucine, phenylalanine, tyrosine, histidine, or tryptophan is included, the concentration of citrulline is less than 1 times that of the lowest-concentration amino acid of leucine, isoleucine, phenylalanine, tyrosine, histidine, or tryptophan.

9. The external standard solution according to claim 8 , comprising valine and at least one of leucine and isoleucine;
wherein valine has a concentration of 0.0003 M to 0.49 M;
wherein if leucine is included in the external standard solution, its concentration is 0.1 to less than 1.0 times the concentration of valine; and
wherein if isoleucine is included in the external standard solution, its concentration is 0.05 to 0.7 times the concentration of valine.

10. The external standard solution according to claim 9 , further comprising at least one of phenylalanine and tyrosine;
wherein if phenylalanine is included in the external standard solution, its concentration is 0.1 to 0.6 times the concentration of valine; and
wherein if tyrosine is included in the external standard solution, its concentration is 0.1 to 0.7 times the concentration of valine.

11. The external standard solution according to claim 10 , further comprising at least one of histidine and tryptophan;
wherein if histidine is included in the external standard solution, its concentration is 0.1 to 0.8 times the concentration of valine; and
wherein if tryptophan is included in the external standard solution, its concentration is 0.1 to 0.6 times the concentration of valine, and when leucine, isoleucine, phenylalanine, tyrosine, or histidine is included, the concentration of tryptophan is less than 1 times that of the lowest-concentration amino acid of leucine, isoleucine, phenylalanine, tyrosine, or histidine.

12. The external standard solution according to claim 11 , further comprising citrulline;
wherein the concentration of citrulline is 0.01 to 0.3 times the concentration of valine, and when leucine, isoleucine, phe

Assignees

• Hayakawa Masako
• Shimbo Kazutaka
• Yoshida Hiroo
• Wako Pure Chem Ind Ltd
• Ajinomoto Kk

Inventors

• Hayakawa Masako
• Shimbo Kazutaka
• Yoshida Hiroo

Classifications

• G01N2030/042

  Standards · CPC title

• Y10T436/106664

  Blood serum or blood plasma standard or control · CPC title

• G01N33/6848

  Methods of protein analysis involving mass spectrometry · CPC title

• G01N33/6806

  Determination of free amino acids · CPC title

• G01N33/96 Primary

  involving blood or serum control standard · CPC title