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Patent US5938932A successfully refreshed from Google Patents.
US5938932A
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High-throughput method and apparatus for identifying, quantitating and determining the purity of chemical compounds in mixtures
Assignee: Pharmacopeia Drug Discovery Inc
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Filing: 1997-11-14
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Granted: 1999-08-17
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Expires: 2017-11-14
Abstract
Abstract A method and apparatus for high-throughput identity confirmation, quantitation and purity determination of a compound of interest in a mixture of compounds is disclosed. According to the method, a chemical mixture, such as may be obtained from a chemical library, is processed to obtain a stream having a time-varying composition, such as by using a high pressure liquid chromatograph. The stream is split into two portions or streams for substantially contemporaneous detection in a compound-identifying device, such as a mass spectrograph, and in a compound-quantitating device, such as an evaporative light scattering detector. A peak in a chromatogram obtained from the compound-quantitating device is identified as the compound of interest by cross-correlation, via elution time, with chromatographic results obtained from the compound-identifying device. Once the peak is identified as corresponding to the compound of interest, the corresponding peak area is used for quantitation and purity determination.
Inventors
- 👤 James A. Connelly
- 👤 Linda O'Brien
- 👤 Sue Xiuqing Zhang
- 👤 Ning Zhao
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 03:30
CPC Classifications
G; G01; G01N; G01N30/00; G01N30/02; G01N30/80; G01N30/82; G01N30/86; G01N30/8675; G01N30/8679; B; B01; B01J; B01J2219/00; B01J2219/00274; B01J2219/0068; B01J2219/00702; B01J2219/00707; G01N30/62; G01N30/72; G01N30/78; G01N30/8624; G01N30/8631; G01N35/00; G01N35/08
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
220 words
A method for identifying and quantitating at least a first compound in a mixture having a plurality of compounds, comprising the steps of: (A) separating the compounds, the separated compounds forming an eluent having a time-varying composition, the eluent representable by a chromatogram having a plurality of positionally-separated peaks extending above a baseline, the peaks corresponding to the compounds of the mixture, the position of each peak corresponding to an elution time for a corresponding compound; (B) splitting the eluent into a first portion that is delivered to a compound-identifying device and a second portion that is delivered to a compound quantitating/purity-determining device; (C) detecting a first compound in the first portion using the compound-identifying device, representing the first compound as a first peak extending above a baseline and having a first elution time in a first chromatogram, and identifying the first peak as corresponding to the first compound; (D) detecting the first compound in the second portion using the compound quantitating/purity-determining device, representing the first compound as a second peak extending above a baseline and having a second elution time in a second chromatogram, and determining that the second peak corresponds to the first compound; and (E) quantitating the first compound using the second peak; wherein, the first compound in the first and second portions are detected substantially contemporaneously.
Claim 2
Independent Claim
220 words
A method for identifying and quantitating at least a first compound in a mixture having a plurality of compounds, comprising the steps of: (A) separating the compounds, the separated compounds forming an eluent having a time-varying composition, the eluent representable by a chromatogram having a plurality of positionally-separated peaks extending above a baseline, the peaks corresponding to the compounds of the mixture, the position of each peak corresponding to an elution time for a corresponding compound; (B) splitting the eluent into a first portion that is delivered to a compound-identifying device and a second portion that is delivered to a compound quantitating/purity-determining device; (C) detecting a first compound in the first portion using the compound-identifying device, representing the first compound as a first peak extending above a baseline and having a first elution time in a first chromatogram, and identifying the first peak as corresponding to the first compound; (D) detecting the first compound in the second portion using the compound quantitating/purity-determining device, representing the first compound as a second peak extending above a baseline and having a second elution time in a second chromatogram, and determining that the second peak corresponds to the first compound; and (E) quantitating the first compound using the second peak; wherein, the first compound in the first and second portions are detected substantially contemporaneously.
Claim 3
Dependent Claim
40 words
The method of claim 1, wherein step (D) comprises determining that the second peak corresponds to the first compound by matching the second elution time to the first elution time, the first and second elution times being substantially the same.
Claim 4
Dependent Claim
53 words
The method of claim 2, wherein step (A) comprises adsorbing the compounds of the mixture on to a solid stationary phase and desorbing the compounds of the mixture from the solid stationary phase, wherein each compound in the mixture adsorbs/desorbs at a unique rate, thereby determining a unique elution time for each compound.
Claim 5
Dependent Claim
44 words
The method of claim 3, wherein the operations of adsorbing the compounds of the mixture onto a solid stationary phase and desorbing the compounds of the mixture from the solid stationary phase comprise separating the compounds of the mixture using high performance liquid chromatography.
Claim 6
Dependent Claim
34 words
The method of claim 2, wherein step (E) comprises quantitating the first compound by determining the area under the second peak, and further determining the area under other peaks appearing in the second chromatogram.
Claim 7
Dependent Claim
71 words
The method of claim 5, further comprising correlating the area under the second peak and said other peaks to mass, and determining a purity of the first compound according to the expression: P=(m i /Σm i )×100, wherein P is the percentage purity of the first compound, m i is the mass of the first compound in the mixture, and Σm i is the mass of all compounds in the mixture.
Claim 8
Dependent Claim
26 words
The method of claim 1, wherein step (C) comprises using a mass spectrometer for detecting the first compound and confirming its identity as the first compound.
Claim 9
Dependent Claim
20 words
The method of claim 1, wherein step (D) comprises using an evaporative light scattering detector for detecting the first compound.
Claim 10
Dependent Claim
46 words
The method of claim 1, wherein, step (B) comprises splitting the eluent so that no more than about 25 weight percent of the eluent is apportioned to the first portion, and at least about 75 volume percent of the eluent is apportioned to the second portion.
Claim 11
Dependent Claim
25 words
The method of claim 1, and further comprising the step of using a UV detector to obtain spectral absorbance data for compounds in the eluent.
Claim 12
Independent Claim
174 words
A method for correlating the identity of a first compound in a first mixture of compounds between different analytical devices, comprising the steps of: (A) forming a second mixture having a time-varying composition, the second mixture comprising the same compounds as the first mixture; (B) splitting the second mixture into a first and a second portion, the first and second portions having the same time-varying composition; (C) detecting the first compound in the first portion using a first analytical device, representing the first compound as a first peak extending above a baseline and having a first elution time in a first chromatogram, and identifying the first peak as corresponding to the first compound; (D) detecting the first compound in the second portion using a second analytical device, representing the first compound as a second peak extending above a baseline and having a second elution time in a second chromatogram, and determining that the second peak corresponds to the first compound; wherein, the first compound in the first and second portions are detected substantially contemporaneously.
Claim 13
Independent Claim
174 words
A method for correlating the identity of a first compound in a first mixture of compounds between different analytical devices, comprising the steps of: (A) forming a second mixture having a time-varying composition, the second mixture comprising the same compounds as the first mixture; (B) splitting the second mixture into a first and a second portion, the first and second portions having the same time-varying composition; (C) detecting the first compound in the first portion using a first analytical device, representing the first compound as a first peak extending above a baseline and having a first elution time in a first chromatogram, and identifying the first peak as corresponding to the first compound; (D) detecting the first compound in the second portion using a second analytical device, representing the first compound as a second peak extending above a baseline and having a second elution time in a second chromatogram, and determining that the second peak corresponds to the first compound; wherein, the first compound in the first and second portions are detected substantially contemporaneously.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2002-08-16 | 2003-02-15 | 2003-08-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-08-16 | 2007-02-15 | 2007-08-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-08-16 | 2011-02-15 | 2011-08-17 | $7700.00 | Window Closed / Lapsed |