Method and apparatus for impurity detection

• US 6,629,039 B1
• Filed: 04/27/2000
• Issued: 09/30/2003
• Est. Priority Date: 04/27/2000
• Status: Expired due to Fees

• Current Assignee: Perkinelmer Instruments LLC (Revvity, Inc.)
• Original Assignee: Perkinelmer Instruments LLC (Revvity, Inc.)
• Inventors: Wang, Yongdong
• Primary Examiner(s): Barlow, John
• Assistant Examiner(s): BHAT, ADITYA S
• Application Number:
  US09/561,600
• Time in Patent Office: 1,251 Days
• Field of Search: 702/22, 422/70, 422/56, 73/310.3
• US Class Current: 702/22
• CPC Class Codes: G01N 30/74 Optical detectors measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J
• CPC Class Codes: G01N 30/8644 Data segmentation, e.g. time windows
• CPC Class Codes: G01N 30/8689 Peak purity of co-eluting compounds

Abstract

A method and apparatus is provided for detecting an impurity in a sample where an index can be calculated to assess purity in the presence of n major components with signal averaging or noise-filtering automatically built-in. The method and apparatus can be applied to liquid chromatography impurity detection using UV-VIS spectrophotometry based on robust matrix algebra representing the entire spectral space generated by the sample.

Claims

1. An apparatus for detecting an impurity in a sample having at least one component comprising:

a device for obtaining characteristic measurements for the sample;

a computer linked to said device;

software executing on said computer for selecting a value representing an anticipated number of components in the sample;

software executing on said computer for generating a matrix representing said characteristic measurements for the sample, said characteristic measurements having at least two variables in each dimension;

software executing on said computer for repeatedly selecting a subset within said matrix for analysis of the relation between the component and impurity;

software executing on said computer for constructing a projection matrix by projecting each of said characterstic measurements of said matrix onto said subset to calculate a residual error; and

software executing on said computer for calculating an index from said subset to assess purity of the sample.

2. The apparatus of claim 1 wherein said characteristic measurement contains a baseline component.

3. The apparatus of claim 1 wherein said characteristic measurement does not contain a baseline component.

4. The apparatus of claim 1 wherein said characteristic measurements are spectra associated with a chromatographic peak.

5. The apparatus of claim 1 wherein said subset is represented by sub-matrix R_j having values which can be decomposed into the expression:

6. The apparatus of claim 4 wherein said matrix is dimensioned with data representing retention times for the chromatographic peak and wavelengths for the spectra.

7. The apparatus of claim 1 further comprising software executing on said computer for calculating a residual error e according to the equation:

8. The apparatus of claim 5 wherein said sub-matrix R_j changes its said values as it moves consecutively from one set of p columns to another such that said sub-matrix R_j is formed by taking the [j−

(p−

1)/2] th to [j+(p−

1)/2] th column of said matrix represented by R, for each j where (p−

1)/2+1≧

j≧

n−

(p−

1)/2.

9. The apparatus of claim 1 wherein said index represents a purity index.

10. The apparatus of claim 1 wherein said index represents an impurity index.

11. The apparatus of claim 10, wherein said impurity index is represented by E according to the equation:

$E=\sqrt{\frac{e^T<br><br>e}{n-r_0-r_1}}.$

12. The apparatus of claim 9 wherein said purity index is represented by k_j and is calculated from S_j according to the equation:

$k_j=\frac{\underset{i=1}{\overset{r_0+r_1}{\sum <br><br>}}<br><br>\text{\hspace{1em}<br><br>}<br><br>S_i}{S_r}.$