System for analysis of phase-I and phase-II metabolites and parent compounds without hydrolysis

Patent metadata

Field	Value
Publication number	US-9404900-B2
Application number	US-201213724316-A
Country	US
Kind code	B2
Filing date	Dec 21, 2012
Priority date	Dec 21, 2012
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

An apparatus comprises: a first chromatographic column fluidically coupled to a source of sample and a source of a first chromatographic mobile phase solvent; a second chromatographic column fluidically coupled to the first column; a source of a second mobile phase solvent fluidically coupled between the first and second columns; and a detector, the first chromatographic column being configurable to receive, in a trapping step, the first solvent and sample and to retain a first portion of a plurality of analytes therein and to pass a second portion of the plurality of analytes therethrough, the second chromatographic column being configurable, in the trapping step, to receive the second portion of the plurality of analytes and the first and second solvents and to retain the second portion of the plurality of analytes therein, the detector being arranged to receive the second and first portions in respective first and second elution steps.

First claim

What is claimed is:

1. An automated sample preparation and analysis system comprising:
(a) an automated sample preparation station for preparing a plurality of samples in accordance with a plurality of assays;
(b) a sample analysis station for automatically performing the plurality of assays; and
(c) a transport mechanism for transporting prepared samples from the sample preparation station to the sample analysis station,
wherein the sample analysis station comprises:
(i) a first supply of chromatographic mobile phase;
(ii) a second supply of chromatographic mobile phase;
(iii) a first chromatographic column comprising an outlet end and an inlet end that is configured to receive a chromatographic mobile phase from the first supply and a portion of a prepared sample;
(iv) a second chromatographic column comprising an inlet end and an outlet end;
(v) at least one valve or tee-junction having a first outlet port fluidically coupled to the second chromatographic column inlet end, a second outlet port, a first inlet port fluidically coupled to the first chromatographic column outlet end and a second inlet port fluidically coupled to the second supply of chromatographic mobile phase;
(vi) a mass spectrometer; and
(vii) a multi-port valve comprising a first inlet port of the multi-port valve fluidically coupled to the second outlet port of the valve or tee-junction, a second inlet port of the multi-port valve fluidically coupled to the second chromatographic column outlet end, and an outlet port of the multi-port valve fluidically coupled to the mass spectrometer;
wherein the at least one valve or tee-junction and the multi-port valve are mutually configurable such that:
in a trapping configuration, the second chromatographic column inlet end is fluidically coupled to both the first chromatographic column outlet end and the second supply of chromatographic mobile phase and the second chromatographic column outlet end is fluidically coupled to a waste line;
in a first elution configuration, the second chromatographic column inlet end is fluidically coupled to the second supply of chromatographic mobile phase and the second chromatographic column outlet end is fluidically coupled to the mass spectrometer; and
in a second elution configuration, the first chromatographic column outlet end is fluidically coupled to the mass spectrometer and the second chromatographic column outlet end is fluidically coupled to the waste line.

2. An automated sample preparation and analysis system as recited in claim 1 , wherein the first and second chromatographic columns comprise different respective stationary phases.

3. An automated sample preparation and analysis system as recited in claim 1 , wherein one of the two chromatographic columns performs analyte separation by hydrophilic interaction (HILIC) chromatography and the other of the two columns performs analyte separation by reversed-phase chromatography.

4. An automated sample preparation and analysis system as recited in claim 1 , wherein the at least one valve or tee-junction comprises:
a selection valve comprising:
the first inlet port of the at least one valve or tee-junction;
the second outlet port of the at least one valve or tee-junction; and
a selection valve outlet port; and

a gradient valve or tee-junction comprising:
the second inlet port of the at least one valve or tee-junction;
the first outlet port of the at least one valve or tee-junction; and
a third inlet port of the at least one valve or tee-junction fluidically coupled to the selection valve outlet port.

5. An automated sample preparation and analysis system as recited in claim 1 , wherein the at least one valve or tee-junction comprises a second multi-port valve comprising:
the first outlet port of the at least one valve or tee-junction;
the first inlet port of the at least one valve or tee-junction;
the second outlet port of the at least one valve or tee-junction; and
the second inlet port of the at least one valve or tee-junction,
wherein the second multi-port valve is configured to mix fluids received at the first and second inlet ports of the at least one valve or tee-junction and to deliver the mixture to the second outlet port of the at least one valve or tee-junction.

6. An automated sample preparation and analysis system as recited in claim 1 , wherein each of the first and second supplies of chromatographic mobile phase comprises:
a source of a first chromatographic mobile phase solvent;
a source of a second chromatographic mobile phase solvent;
a gradient valve fluidically coupled to the source of the first chromatographic mobile phase solvent and to the source of the second chromatographic mobile phase solvent; and
a fluidic pump fluidically coupled to the gradient valve.

7. An automated sample preparation and analysis system comprising:
(a) an automated sample preparation station for preparing a plurality of samples in accordance with a plurality of assays;
(b) a sample analysis station for automatically performing the plurality of assays; and
(c) a transport mechanism for transporting prepared samples from the sample preparation station to the sample analysis station,
wherein the sample analysis station comprises:
(i) a first supply of chromatographic mobile phase;
(ii) a second supply of chromatographic mobile phase;
(iii) a tee-junction or first valve that is configured to receive a first fluid comprising a chromatographic mobile phase from the first supply and a portion of a prepared sample and to divide the first fluid into a first portion and a second portion;
(iv) a second valve configured to receive a second fluid comprising a chromatographic mobile phase from the second supply and to divide the second fluid into a first portion and a second portion;
(v) a first chromatographic column comprising an outlet end and an inlet end configured to receive the first portion of the first fluid and the first portion of the second fluid;
(vi) a second chromatographic column comprising an outlet end and an inlet end configured to receive the second portion of the first fluid and the second portion of the second fluid;
(vii) a mass spectrometer; and
(viii) a third valve coupled between the mass spectrometer and both of the outlet end of the first chromatographic column and the outlet end of the second chromatographic column.

8. An automated sample preparation and analysis system as recited in claim 7 , wherein the first and second chromatographic columns comprise different respective stationary phases.

9. An automated sample preparation and analysis system as recited in claim 7 , wherein the third valve is operable to direct, to the mass spectrometer, either exclusively an outflow from the outlet end of the first chromatographic column or exclusively an outflow from the outlet end of the second chromatographic column.

10. An automated sample preparation and analysis system as recited in claim 1 , wherein the second chromatographic column comprises a unique inlet end and a unique outlet end.

Assignees

• Herman Joseph
• Fair Sarah J
• Argoti Dayana
• Thermo Finnigan Llc

Inventors

• Herman Joseph
• Fair Sarah J
• Argoti Dayana

Classifications

• G01N30/468

  involving switching between different column configurations · CPC title

• G01N30/08

  using an enricher · CPC title

• G01N30/462 Primary

  with different eluents or with eluents in different states (G01N30/463 takes precedence) · CPC title

• G01N2030/628

  Multiplexing, i.e. several columns sharing a single detector · CPC title

• G01N2030/143

  selective absorption · CPC title