Systems, methods and devices for width-based analysis of peak traces

Patent metadata

Field	Value
Publication number	US-10634653-B2
Application number	US-201715824962-A
Country	US
Kind code	B2
Filing date	Nov 28, 2017
Priority date	Nov 28, 2016
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

Systems, methods and devices are taught for providing analytical methods for peak-shaped responses separated in time or space, including quantitation of chromatographic peaks based on a width measurement of a peak trace at a selected height as a quantitation element. Methods of treating a peak trace as a composition of exponential functions representing a leading and a trailing end are included. Methods that facilitate the detection of impurities in peak trace outputs are also included.

First claim

The invention claimed is:

1. A method of chromatographic quantitation of an analyte, comprising:
a) flowing the analyte at least at a first concentration, a second concentration, and then a third concentration into a chromatographic column;
b) detecting the analyte at the first concentration, the second concentration, and the third concentration coming out from the chromatographic column by using a chromatographic detector;
c) obtaining a first, second, and third signal curves from the chromatographic detector, the first, second, and third signal curves being a representation of the analyte at the first, second, and third concentrations, respectively, detected by the chromatographic detector;
d) measuring a width of a peak in each of the first, second, and third signal curves at a plurality of peak heights;
e) calculating a plurality of calibration equations based on the first, second, third concentrations and the measured peak widths for each of the plurality of peak heights; and
f) identifying one of the plurality of peak heights that provides the calibration equation having a lowest error.

2. The method of claim 1 , wherein the width is determined by using a width-based quantitation algorithm comprising: W h =p(ln h ) q , wherein W h is the width at absolute height h of the peak, h is h max /h, h max is the peak amplitude of the peak, and p and q are constants.

3. The method of claim 1 , further comprising;
g) flowing a sample into the chromatographic column, the sample including the analyte;
h) detecting the analyte of the sample coming out from the chromatographic column by using the chromatographic detector;
i) obtaining a signal curve of the sample from the chromatographic detector, detected by the chromatographic detector;
j) measuring a width of a peak in the signal curve of the sample at the identified peak height; and
k) determining a concentration of the analyte of the sample using the calculated calibration equation with the identified peak height, the calculated calibration equation having a form of: ln C=aW h n +b, wherein W h is the width at absolute height h of the peak, wherein C is a concentration of the analyte, and further wherein n, a, and b are constants.

4. The method of claim 1 , further comprising a suppressor coupled with the chromatographic column for receiving an output from the chromatographic column, wherein the suppressor is coupled with the chromatographic detector, such that an output from the suppressor is detected by the chromatographic detector.

5. A method of detecting an impurity in chromatography, comprising:
a) flowing an analyte of a sample through a chromatographic column;
b) detecting a concentration of the analyte coming out from the chromatographic column by using a chromatographic detector;
c) obtaining a first signal curve from the chromatographic detector, the first signal curve being a representation of the concentration of the analyte detected by the chromatographic detector;
d) measuring a first peak width W h1 at a first absolute peak height h 1 , a second peak width W h2 at a second absolute peak height h 2 , and a third peak width W h3 at a third absolute peak height h 3 of a peak in the first signal curve, wherein the first absolute peak height h 1 , the second absolute peak height h 2 , and the third absolute peak height h 3 are different;
e) determining a peak shape index ratio of the sample of the peak in the first signal curve with a formula comprising ln(W h1 /W h2 )/ln(W h2 /W h3 ); and
f) identifying a presence of the impurity in the sample where the determined peak shape index ratio of the peak in the first signal curve differs from a peak shape index ratio of a standard sample.

6. The method of claim 5 further comprising:
g) flowing the analyte of the standard sample through the chromatographic column;
h) detecting a concentration of the analyte of the standard sample coming out from the chromatographic column by using the chromatographic detector;
i) obtaining a second signal curve from the chromatographic detector, the second signal curve being a representation of the concentration of the analyte of the standard sample detected by the chromatographic detector;
j) measuring the first peak width W h1 at the first absolute peak height h 1 , the second peak width W h2 at the second absolute peak height h 2 , and the third peak width W h3 at the third absolute peak height h 3 of a peak in the second signal curve, wherein the first absolute peak height h 1 , the second absolute peak height h 2 , and the third absolute peak height h 3 are different; and
k) determining the peak shape index ratio of the standard sample of the peak in the second signal curve with the formula.

7. The method of claim 6 further comprising:
l) repeating the steps g) and k) on multiple injections of the standard sample;
m) calculating a confidence range of the peak shape index ratio at a confidence level above 90% for the standard sample; and
n) identifying the presence of the impurity in the sample where the determined peak shape index ratio of the sample is outside of the calculated confidence range.

8. The method of claim 6 , wherein the peak of the standard sample and the analyte peak of the sample under test have a same maximum peak height.

9. The method of claim 5 , further comprising a suppressor coupled with the chromatographic column for receiving an output from the chromatographic column, wherein the suppressor is coupled with the chromatographic detector, such that an output from the suppressor is detected by the chromatographic detector.

10. A method of detecting an impurity in chromatography, comprising:
a) flowing an analyte of a sample through a chromatographic column;
b) detecting a concentration of the analyte coming out from the chromatographic column by using a chromatographic detector;
c) obtaining a first signal curve from the chromatographic detector, the first signal curve being a representation of the concentration of the analyte detected by the chromatographic detector;
d) measuring a first peak width W h1 at a first absolute peak height h 1 , a second peak width W h2 at a second absolute peak height h 2 , a third peak width W h3 at a third absolute peak height h 3 , and a fourth peak width W h4 at a fourth absolute peak height h 4 of a peak in the first signal curve, wherein the first absolute peak height h 1 , the second absolute peak height h 2 , the third absolute peak height h 3 , and the fourth absolute peak height h 4 are different;
e) determining a peak shape index ratio of the sample of the peak in the first signal curve with a formula comprising: ln(W h1 /W h2 )/ln(W h3 /W h4 ); and
f) identifying a presence of the impurity in the sample where the determined peak shape index ratio of the peak in the first signal curve differs from a peak shape index ratio of a standard sample.

11. The method of claim 10 further comprising:
g) flowing the analyte of the standard sample through the chromatographic column;
h) detecting a concentration of the analyte of the standard sample coming out from the chromatographic column by using the chromatographic detector;
i) obtaining a second signal curve from the chromatographic detector, the second signal curve being a representation of the concentration of the analyte of the standard sample detected by the chromatographic detector;
j) measuring the first peak width W h1 at the first absolute peak height h 1 , the second peak width W h2 at the second absolute peak height h 2 , the third peak width W h3 at the third absolute peak height h 3 , and the fourth peak width W h4 at the fourth absolute peak height h 4 of a peak in the

Assignees

• Univ Texas
• Dionex Corp

Inventors

• Dasgupta Purnendu K
• Kadjo Akinde F
• Srinivasan Kannan

Classifications

• G01N2030/025

  Gas chromatography · CPC title

• B01D15/161 Primary

  Temperature conditioning · CPC title

• G01N2030/027

  Liquid chromatography · CPC title

• B01D15/163

  Pressure or speed conditioning · CPC title

• G01N30/30

  of temperature · CPC title