Device for quantitative analysis of a drug or metabolite profile
A device, in particular a sample preparation device for the quantitative analysis of a drug and/or metabolite profile in a biological sample, which includes an insert for such a device being impregnated with at least one internal standard, to the internal standard itself, and to a kit comprising the device. Further, the invention also relates to an apparatus containing the device, and to a method for the quantitative analysis of a drug and/or metabolite profile in a biological sample employing the device.
1. A device for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(A) one or more wells,
(B) one or more inserts located in the wells, wherein the insert comprises:
(a) a support comprising a sorbent material for liquids with which the support is impregnated, and
(b) at least one organic internal standard being encapsulated with a covering material protecting the internal standard from degradation and chemical reactivity prior to use, wherein the covering material comprises at least one of a micelle-forming compound, a liposome-forming compound, a polyhydroxy compound, a polymer selected from polyalkylene glycol homopolymers or copolymers or mixtures thereof, and
(C) a retainer holding the insert within the well with a distance between the insert and the the walls and the bottom of the well in order to allow a free circulation of fluids around the insert.
2. The device according to claim 1 , wherein the sorbent material comprises at least one of a cellulose material, glass fibres, glass beads, polyacrylamide gel, porous plastic inert polymer or porous graphite.
3. The device according to claim 1 , wherein the encapsulated standard is microencapsulated.
4. The device according to claim 1 , wherein the polymer is selected from a polyethylene glycol or polypropylene glycol homopolymer or copolymer or a mixture thereof.
5. The device according to claim 4 , wherein the polymer is PEG 1000.
6. The device according to claim 1 , wherein the polyhydroxy compound is selected from sorbitol or glycerol.
7. The device according to claim 1 , wherein the micelle-forming compound is a surfactant.
8. The device according to claim 1 , wherein the liposome forming compound is a phospholipid.
9. The device according to claim 8 , wherein the phosopholipid is a phosphatidyl choline or a phosphatidyl ethanolamine or derivatives thereof.
10. The device according to claim 1 , wherein the one or more wells comprise a filter for separating micron size solids, and an outlet for discharging the filtrate.
11. The device according to claim 10 , wherein the filter is located between the insert and the outlet.
12. The device according to claim 10 , wherein the outlet opens under applied centrifugal force or reduced pressure.
13. A device for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(A) one or more wells;
(B) one or more inserts located in the wells, wherein the insert comprises
(a) a support comprising a sorbent material for liquids which support is impregnated with
(b) at least one organic internal standard; and
(C) a retainer holding the insert within the well with a distance between the insert and the walls and the bottom of the well in order to allow a free circulation of fluids around the insert.
14. The device according to claim 13 , wherein the one or more wells comprise a filter for separating micron size solids, and an outlet for discharging the filtrate.
15. The device according to claim 14 , wherein the filter is located between the insert and the outlet.
16. The device according to claim 14 , wherein the outlet ( 5 ) opens under applied centrifugal force or reduced pressure.
17. A device for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(A) one or more wells;
(B) one or more inserts located in the wells, wherein the insert comprises:
(a) a support comprising a sorbent material for liquids which support is impregnated with
(b) at least one organic internal standard being encapsulated with a covering material protecting the internal standard from degradation and chemical reactivity prior to use, wherein the covering material comprises at least one of a micelle-forming compound, a liposome-forming compound, a polyhydroxy compound, and a polymer selected from polyalkylene glycol homopolymers or copolymers or mixtures thereof; and
(C) a retainer holding the insert within the well with a distance between the insert and the the walls and the bottom of the well in order to allow a free circulation of fluids around the insert.
18. A kit for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising the device as defined in claim 1 .
19. A kit for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising the device as defined in claim 13 .
20. A kit for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising the device as defined in claim 17 .
21. An apparatus for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(a) a treatment unit for preparing the drugs and/or metabolites to be screened comprising
(a1) an automated liquid handling system, and
(a2) at least one device as defined in claim 1 for derivatization of the drugs and/or metabolites present in the sample and for subsequent extraction of the derivatives;
(b) a mass spectrometer for the quantitative targeted mass spectrometry-based analysis, and
(c) a database for storing results of the analysis.
22. An apparatus for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(a) a treatment unit for preparing the drugs and/or metabolites to be screened comprising
(a1) an automated liquid handling system, and
(a2) at least one device as defined in claim 13 for derivatization of the drugs and/or metabolites present in the sample and for subsequent extraction of the derivatives;
(b) a mass spectrometer for the quantitative targeted mass spectrometry-based analysis, and
(c) a database for storing results of the analysis.
23. An apparatus for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(a) a treatment unit for preparing the drugs and/or metabolites to be screened comprising
(a1) an automated liquid handling system, and
(a2) at least one device as defined in claim 17 for derivatization of the drugs and/or metabolites present in the sample and for subsequent extraction of the derivatives;
(b) a mass spectrometer for the quantitative targeted mass spectrometry-based analysis, and
(c) a database for storing results of the analysis.
24. A device comprising:
a support comprising a sorbent material;
a plurality of mass spectrometry, organic, metabolite standards of known amounts impregnated in the support and dried; and
a well and a retainer, wherein the retainer holds the support within the well.
25. The device of claim 24 , wherein the mass spectrometry, organic, metabolite standards comprise amino acids labelled with stable isotopes.
26. The device of claim 24 , wherein the mass spectrometry, organic, metabolite standards comprise polypeptides labelled with stable isotopes.
27. The device of claim 24 , wherein the mass spectrometry, organic, metabolite standards comprise lipids labelled with stable isotopes.
28. The device of claim 24 , wherein the mass spectrometry, organic, metabolite standards comprise acylcarnitines labelled with stable isotopes.
29. A device for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(A) one or more wells, wherein the one or more wells comprise a filter for separating micron size solids, and an outlet for discharging the filtrate; and
(B) one or more inserts located in the wells, wherein the insert comprises:
(a) a support comprising a sorbent material for liquids with which the support is impregnated, and
(b) at least one organic internal standard being encapsulated with a covering material protecting the internal standard from degradation and chemical reactivity prior to use, wherein the covering material comprises at least one of a micelle-forming compound, a liposome-forming compound, a polyhydroxy compound, a polymer selected from polyalkylene glycol homopolymers or copolymers or mixtures thereof, wherein the filter is located between the insert and the outlet.
30. A device for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(A) one or more wells, wherein the one or more wells comprise a filter for separating micron size solids, and an outlet for discharging the filtrate and the outlet opens under applied centrifugal force or reduced pressure; and
(B) one or more inserts located in the wells, wherein the insert comprises:
(a) a support comprising a sorbent material for liquids with which the support is impregnated, and
(b) at least one organic internal standard being encapsulated with a covering material protecting the internal standard from degradation and chemical reactivity prior to use, wherein the covering material comprises at least one of a micelle-forming compound, a liposome-forming compound, a polyhydroxy compound, a polymer selected from polyalkylene glycol homopolymers or copolymers or mixtures thereof.
31. A device for the quantitative analysis of a drug and/or a metabolite profile in a biological sample, comprising:
(A) one or more wells,
(B) one or more inserts located in the wells, wherein the insert comprises:
(a) a support comprising a sorbent material for liquids with which the support is impregnated, and
(b) at least one organic internal standard being encapsulated with a covering material protecting the internal standard from degradation and chemical reactivity prior to use, wherein the covering material consists of at least one of a micelle-forming compound, a liposome-forming compound, a polyhydroxy compound, a polymer selected from polyalkylene glycol homopolymers or mixtures thereof.