EP1242801A1 - Inert carriers - Google Patents

Inert carriers

Info

Publication number
EP1242801A1
EP1242801A1 EP00979766A EP00979766A EP1242801A1 EP 1242801 A1 EP1242801 A1 EP 1242801A1 EP 00979766 A EP00979766 A EP 00979766A EP 00979766 A EP00979766 A EP 00979766A EP 1242801 A1 EP1242801 A1 EP 1242801A1
Authority
EP
European Patent Office
Prior art keywords
compound
carrier
compounds
metal surface
metal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00979766A
Other languages
German (de)
French (fr)
Inventor
Anthony Corless
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
AstraZeneca AB
Original Assignee
AstraZeneca AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by AstraZeneca AB filed Critical AstraZeneca AB
Publication of EP1242801A1 publication Critical patent/EP1242801A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J4/00—Feed or outlet devices; Feed or outlet control devices
    • B01J4/02—Feed or outlet devices; Feed or outlet control devices for feeding measured, i.e. prescribed quantities of reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3204—Inorganic carriers, supports or substrates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3234—Inorganic material layers
    • B01J20/3236—Inorganic material layers containing metal, other than zeolites, e.g. oxides, hydroxides, sulphides or salts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00504—Pins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00513—Essentially linear supports
    • B01J2219/00515—Essentially linear supports in the shape of strings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00513—Essentially linear supports
    • B01J2219/00518—Essentially linear supports in the shape of tapes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the invention relates to adsorbing chemical samples onto metallic carrier materials for long term storage of compounds in, for example, a proprietary compound collection.
  • Compound collections are used in the search for agents with novel pharmaceutical, agrochemical or other fine chemical applications and are a valuable source of structural and chemical diversity used in identifying new leads as potential inhibitors of a biological target.
  • Compound collections may contain more than 100,000 different compounds and due to increasingly efficient compound acquisition, either through commercial sources, or by high throughput synthesis, compound collections with more than 1 million different compounds are now of a typical size in some research organisations.
  • High throughput multiple parallel synthesis can generate very large numbers of individual compounds, typically 100-5000 per week, but the sample size is usually small, ⁇ 100mg.
  • To try and obtain all or most of these samples as crystalline or amorphous powders using the methods normally available to chemists would increase the overall synthesis time to such an extent that the HTMPS process would be impractical.
  • compounds from HTMPS are stored sometimes as dry films or as solutions, usually in dimethyl sulphoxide (DMSO). The dispensing of compounds stored as dry films is often very difficult, and the difficulty increases significantly as the sample size decreases.
  • DMSO dimethyl sulphoxide
  • HTS high throughput screening
  • a whole compound collection of , for example, 100,000 compounds may be screened in a number of days against a new biological target, using automated or semi-automated procedures.
  • HTS high throughput screening
  • a typical sample size of compound sample needed to be dispensed for HTS may be less than 0.1 mg, but despite weight variations of ⁇ 10% being tolerated for the purposes of screening, including HTS, it is not practicable to rapidly dispense such small sample sizes.
  • US5519 218 describes sample holders, which are cheap and disposable, for compounds in IR spectroscopy.
  • the sample holders are made from a wire mesh and retain compound in the openings formed by the mesh to allow the IR beam to pass through said compound.
  • the patent does not describe the retrieval of compounds from the mesh and, indeed, disposal of both the holder and compound is preferred due to low cost of the compound holder compared with traditional mineral sample holders for IR spectroscopy, such as KBr plates.
  • a method for storing and dispensing a compound which comprises (1) adsorbing the compound onto a carrier having a metal surface (2)when later required removing the compound from the carrier by contacting liquid, in which the compound is soluble, with the surface of the compound containing carrier and (3) removing the liquid from the carrier.
  • adsorption is achieved from a solution of the compound which is brought into contact with the surface of the carrier and then removing the solvent, for example by evaporation.
  • Extraction of the compound from the carrier may be achieved by contacting the carrier with the compound adsorbed on it with a liquid which is a suitable solvent for the compound , and then removing the carrier from the liquid.
  • the liquid may be separated from the carrier by passing the liquid through or over the metallic surface, or where the metallic surface is in the form of small particles by filtration or magnetism. Where the carrier does not interfere with the assay then it may be left in the assay medium.
  • the compound may be one of any number of different compounds, such as within a compound collection and as such represents a further feature of the invention.
  • Typical liquids in which the compound is soluble and are found in common usage for dissolving compounds for testing are typically either aqueous or organic; aqueous systems may include buffered solutions ; organic solvents include protic solvents, such as ethanol, and aprotic solvents, such as DMSO; alternatively the solvent may be a mixture of any of the above solvents. Additional excipients may be added to the liquid to improve the solubility of the compound.
  • a mat made from a woven mesh of metal fibres, or metal coated non-metal fibres
  • several compounds may be deposited upon zones of the same mat.
  • the solution of the compound is held, when applied to the surface of the mat, within the weave of fibres. Liquid is allowed to freely evaporate leaving compound adsorbed onto the mat in discrete zones.
  • Compound may be recovered, ideally in an automatic way, by passing a volume of liquid known to dissolve the compound through the mat at the zone in which the compound is stored.
  • Such a system lends itself easily to automation where computer controlled systems place compound at predetermined positions, the location being logged, and when that compound is required the computer controlled system revisits that same zone after interrogating the log to retrieve the compounds location and retrieves the material in the manner described above.
  • the same carrier material and the same configuration may be used for the all the compounds, thus leading to a generic use of the technology, or alternatively carriers of the same configuration but in sets of a different material may be used each set being more suited to particular compound types.
  • the configuration of the carrier is the same this also lends easily to the generic use of the technology and, therefore, automation.
  • carriers having a metal surface such as fibre, wire, pin, rod, mesh, grid, sheet or strip
  • Liquid attached to the primer after removal evaporate from the carrier leaving compound adsorbed onto its metal surface.
  • Compound is retrieved by dipping again the carrier into a liquid in which the compound is soluble, or, alternatively, washing the liquid over the carrier.
  • a number of different configurations of the metal surface are anticipated to work.
  • a simple sheet having a metallic surface will work, further treatment of the metal surface could be used, such as to improve the surface area by treatment with such agents to make the surface pitted (such as the use of strong acids), the surface may be contoured so as to form wells or channels through which the liquid may freely flow.
  • Woven metallic fibres may also be used, and are preferred, since these are flexible and may be rolled or even folded, additionally liquid can be forced through the woven materials to recover compound, materials need not be woven but may be a mesh or grid with holes in the sheeting .
  • the carrier may be formed into a free flowing powders by, for example metal fillings.
  • Suitable metal surfaces are those which are stable and are generally inert to most chemical compounds. Examples include, steel, aluminium, chromium, silver, gold etc.
  • a method for storing and dispensing a number of different compounds with different physical properties which comprises (1) adsorbing each compound onto a carrier having a metal surface, (2) storing the adsorbed compounds on the metal surface until a compound is required, (3) extracting the compound from the carrier and (4) dispensing the compound.
  • a further feature of the invention is a method of storing a number of different compounds in a compound collection for an extended duration whilst providing for significant recovery of the compound after storage which comprises adsorption of each compound onto a carrier having a metal surface.
  • a further feature of the invention is a compound collection comprising a number of different compounds wherein each compound has been adsorbed onto a carrier having a metal surface
  • extended duration we mean that we have found that "recovery” (which means >30% w/w , >50 %w/w, ideally >80% w/w, preferably >90%w/w recovery of the sample) of compound may be extracted from the inert carrier even after a period of storage at room temperature of at least 6 months, and in particular over a period of more than 1 year.
  • the "number" of compounds in a compound collection which may be stored by the techniques as described above is not limited by the invention, ideally the invention may be used for storage of compounds in compound collections where the number of different compounds stored may be more than 5, 50, 100, 10 3 , 10" or even more than 10 6 .
  • the invention may also be applied to a subset of a compound collection.
  • compounds By the use of the term "compounds” we refer to compounds which are able to be adsorbed onto carriers. The physical and chemical properties of the compounds are generally unimportant in applying the present invention. However, it will be appreciated that this method is not suited to compounds with low boiling points.
  • Preferred compounds are those stored in compound collections of pharmaceutical, biotechnology or agrochemical companies. Preferred compounds are organic molecules of molecular weight of less than 2000 Daltons, and ideally of 1000 Daltons or less.
  • the carrier adsorbed with a compound provides a material with very similar physical properties even when compounds are adsorbed which have different physical properties. Further advantages include:
  • Compound can be quantitatively and reproducibly adsorbed and extracted from inert carrier; Storage and dispensing of compounds which exist normally as liquids, gums or glasses;
  • Adsorption onto an inert carrier produces metallic material/mesh with very similar handling characteristics
  • Eluents Eluent A: Water containing 50 mM ammonium acetate. (Weigh accurately 3.854 g ammonium acetate and dissolve in 1 litre of
  • Eluent B Methanol containing 43.75 mM ammonium acetate.
  • results 4 are captured in table 1. Also included in the table are the aqueous solubilities of the 13 compounds in 0.1 M phosphate buffer pH 7.4.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to adsorbing chemical samples onto metallic carrier materials for long term storage of compounds in, for example, a proprietary compound collection.

Description

INERT CARRIERS
The invention relates to adsorbing chemical samples onto metallic carrier materials for long term storage of compounds in, for example, a proprietary compound collection.
Large collections of chemical compounds are valuable assets of research organisations. Compound collections are used in the search for agents with novel pharmaceutical, agrochemical or other fine chemical applications and are a valuable source of structural and chemical diversity used in identifying new leads as potential inhibitors of a biological target. Compound collections may contain more than 100,000 different compounds and due to increasingly efficient compound acquisition, either through commercial sources, or by high throughput synthesis, compound collections with more than 1 million different compounds are now of a typical size in some research organisations.
The handling of samples within large compound collections for the purposes of storage, retrieval and testing presents numerous problems. In most organisations samples are obtained and stored as crystalline or amorphous powders and can be dispensed relatively easily by weighing, although this often needs to be done manually because of the varying nature of the solids. Some samples are made or obtained as glassy solids, syrups, oils or liquids and are subsequently stored in these forms. The weighing of these samples is often very time consuming and wasteful.
High throughput multiple parallel synthesis (HTMPS) can generate very large numbers of individual compounds, typically 100-5000 per week, but the sample size is usually small, <100mg. To try and obtain all or most of these samples as crystalline or amorphous powders using the methods normally available to chemists would increase the overall synthesis time to such an extent that the HTMPS process would be impractical. To avoid this problem, compounds from HTMPS are stored sometimes as dry films or as solutions, usually in dimethyl sulphoxide (DMSO). The dispensing of compounds stored as dry films is often very difficult, and the difficulty increases significantly as the sample size decreases. Compounds stored as solutions can be dispensed quickly and accurately, but the manipulation and storage of the solutions subsequent to, and after, dispensing can be very problematical especially in compound handling systems designed to handle solids. In addition, some samples are unstable in solution and decompose on prolonged storage, even at low temperatures.
Increasingly the demands of a compound collection are changing. With the advent of high throughput screening (HTS) a whole compound collection of , for example, 100,000 compounds may be screened in a number of days against a new biological target, using automated or semi-automated procedures. Faced with the need for more rapid dispensing of compounds from the compound collection, the small sample size needed and the large numbers of different sample types existing in a compound collection, current systems of storage and dispensing are increasingly incompatible with modern needs. For example, a typical sample size of compound sample needed to be dispensed for HTS may be less than 0.1 mg, but despite weight variations of ±10% being tolerated for the purposes of screening, including HTS, it is not practicable to rapidly dispense such small sample sizes.
US5519 218 describes sample holders, which are cheap and disposable, for compounds in IR spectroscopy. The sample holders are made from a wire mesh and retain compound in the openings formed by the mesh to allow the IR beam to pass through said compound. The patent does not describe the retrieval of compounds from the mesh and, indeed, disposal of both the holder and compound is preferred due to low cost of the compound holder compared with traditional mineral sample holders for IR spectroscopy, such as KBr plates.
We have found that it is possible to store and retrieve compounds, even after an extended period of storage, by adsorbing the compound onto a carrier. We have found that where the carrier has a metal surface then compounds may be adsorbed onto the metal surface and retrieved, even after an extended period of storage, to recover a significant amount of the compound. A wide variety of compound types may be stored in such a system and therefore the system of storage and retrieval is particularly suited to the pharmaceutical or agrochemical industry where large numbers of compounds of varying physical properties are stored ready for screening against new biological targets.
We present as a first feature of the invention a method for storing and dispensing a compound, which comprises (1) adsorbing the compound onto a carrier having a metal surface (2)when later required removing the compound from the carrier by contacting liquid, in which the compound is soluble, with the surface of the compound containing carrier and (3) removing the liquid from the carrier.
Ideally adsorption is achieved from a solution of the compound which is brought into contact with the surface of the carrier and then removing the solvent, for example by evaporation. Extraction of the compound from the carrier may be achieved by contacting the carrier with the compound adsorbed on it with a liquid which is a suitable solvent for the compound , and then removing the carrier from the liquid. The liquid may be separated from the carrier by passing the liquid through or over the metallic surface, or where the metallic surface is in the form of small particles by filtration or magnetism. Where the carrier does not interfere with the assay then it may be left in the assay medium.
The compound may be one of any number of different compounds, such as within a compound collection and as such represents a further feature of the invention.
Typical liquids in which the compound is soluble and are found in common usage for dissolving compounds for testing are typically either aqueous or organic; aqueous systems may include buffered solutions ; organic solvents include protic solvents, such as ethanol, and aprotic solvents, such as DMSO; alternatively the solvent may be a mixture of any of the above solvents. Additional excipients may be added to the liquid to improve the solubility of the compound. We have found that we may arrange the metallic surfaces into a number of different configurations which may be adapted to more particularly be suited to automation, especially automation of compound recovery from the carrier or automatic deposition of compound onto the carrier, or both. For example, by the use of a mat made from a woven mesh of metal fibres, or metal coated non-metal fibres, several compounds may be deposited upon zones of the same mat. The solution of the compound is held, when applied to the surface of the mat, within the weave of fibres. Liquid is allowed to freely evaporate leaving compound adsorbed onto the mat in discrete zones. Compound may be recovered, ideally in an automatic way, by passing a volume of liquid known to dissolve the compound through the mat at the zone in which the compound is stored. Such a system, lends itself easily to automation where computer controlled systems place compound at predetermined positions, the location being logged, and when that compound is required the computer controlled system revisits that same zone after interrogating the log to retrieve the compounds location and retrieves the material in the manner described above.
The same carrier material and the same configuration may be used for the all the compounds, thus leading to a generic use of the technology, or alternatively carriers of the same configuration but in sets of a different material may be used each set being more suited to particular compound types. However, since the configuration of the carrier is the same this also lends easily to the generic use of the technology and, therefore, automation.
In an alternative arrangement carriers having a metal surface, such as fibre, wire, pin, rod, mesh, grid, sheet or strip, are dipped into solutions of compound and removed. Liquid attached to the primer after removal evaporate from the carrier leaving compound adsorbed onto its metal surface. Compound is retrieved by dipping again the carrier into a liquid in which the compound is soluble, or, alternatively, washing the liquid over the carrier. A number of different configurations of the metal surface are anticipated to work. A simple sheet having a metallic surface will work, further treatment of the metal surface could be used, such as to improve the surface area by treatment with such agents to make the surface pitted (such as the use of strong acids), the surface may be contoured so as to form wells or channels through which the liquid may freely flow. Woven metallic fibres may also be used, and are preferred, since these are flexible and may be rolled or even folded, additionally liquid can be forced through the woven materials to recover compound, materials need not be woven but may be a mesh or grid with holes in the sheeting .The carrier may be formed into a free flowing powders by, for example metal fillings.
Suitable metal surfaces are those which are stable and are generally inert to most chemical compounds. Examples include, steel, aluminium, chromium, silver, gold etc.
Presented as a further feature of the invention is a method for storing and dispensing a number of different compounds with different physical properties which comprises (1) adsorbing each compound onto a carrier having a metal surface, (2) storing the adsorbed compounds on the metal surface until a compound is required, (3) extracting the compound from the carrier and (4) dispensing the compound.
Presented as a further feature of the invention is a method of storing a number of different compounds in a compound collection for an extended duration whilst providing for significant recovery of the compound after storage which comprises adsorption of each compound onto a carrier having a metal surface.
A further feature of the invention is a compound collection comprising a number of different compounds wherein each compound has been adsorbed onto a carrier having a metal surface By use of the term "extended duration" we mean that we have found that "recovery" (which means >30% w/w , >50 %w/w, ideally >80% w/w, preferably >90%w/w recovery of the sample) of compound may be extracted from the inert carrier even after a period of storage at room temperature of at least 6 months, and in particular over a period of more than 1 year.
The "number" of compounds in a compound collection which may be stored by the techniques as described above is not limited by the invention, ideally the invention may be used for storage of compounds in compound collections where the number of different compounds stored may be more than 5, 50, 100, 103, 10" or even more than 106. The invention may also be applied to a subset of a compound collection.
By the use of the term "compounds" we refer to compounds which are able to be adsorbed onto carriers. The physical and chemical properties of the compounds are generally unimportant in applying the present invention. However, it will be appreciated that this method is not suited to compounds with low boiling points. Preferred compounds are those stored in compound collections of pharmaceutical, biotechnology or agrochemical companies. Preferred compounds are organic molecules of molecular weight of less than 2000 Daltons, and ideally of 1000 Daltons or less.
The carrier adsorbed with a compound provides a material with very similar physical properties even when compounds are adsorbed which have different physical properties.. Further advantages include:
Even distribution of compound on inert carrier;
Compound can be quantitatively and reproducibly adsorbed and extracted from inert carrier; Storage and dispensing of compounds which exist normally as liquids, gums or glasses;
Adsorption onto an inert carrier produces metallic material/mesh with very similar handling characteristics;
For the reasons outlined above, robotic handling and weighing of samples is much simpler than for non-adsorbed materials, thereby enabling rapid dispensing of large numbers of compounds; and
Compounds for which only small samples are available can be dispensed far more economically.
The invention is illustrated below by the following no-limiting examples
Examples
Sixteen compounds were selected which spread across physical property space. Parameters considered in the selection were ClogP, molecular volume, number of hydrogen bond donors, number of hydrogen bond acceptors, number of positive charges and number of negative charges. All the parameters were given an equal weighting.
Adsorption of compound onto Inert Supports
10 mM stock solutions in neat DMSO were first made for all 13 compounds. This mimics the format of solubilised compound collection found in many companies. For the stainless steel meshes, pieces of size 150 mm2 by 65 μm thick (approx. vol 0.01 ml) were immersed in each of the sixteen 10 mM DMSO solutions. These were then dried in an oven at 60°C to remove DMSO.
Extraction in to aqueous phosphate buffer (O.IM phosphate) pH 7.4
Extraction was carried out by stirring the support for 72 hrs at 25°C in a vial containing 0.1 M phosphate buffer solution, pH 7.4. The aim was to generate an aqueous solution of concentration 10"5 M, typical of that used in HTS assays. For the stainless steel mesh the calculation is straightforward, we assumed a mesh volume of 0.01 mis, approximately 10 mis of buffer needs to be added. In practise 2 mis was used as a precaution against less adsorption occurring. However the final results were divided by 5 since this turned out not to be the case.
Following 72 hours of stirring the aqueous solutions were analysed using HPLC-UV. The chromatography used is outlined below.
Column: Phenomenex Columbus 3μ C18 30 mm x 2 mm.
Eluents: Eluent A: Water containing 50 mM ammonium acetate. (Weigh accurately 3.854 g ammonium acetate and dissolve in 1 litre of
Milli-Q deionised water.)
Eluent B: Methanol containing 43.75 mM ammonium acetate.
(Weigh accurately 3.372 g ammonium acetate and dissolve in 1 litre methanol (HPLC Gradient grade)). Flow rate: 1.2 ml/min. Temperature: 50°C.
Detection: 5 wavelengths:- 220, 230, 250, 270 and 320 nm. Gradient:
The results 4 are captured in table 1. Also included in the table are the aqueous solubilities of the 13 compounds in 0.1 M phosphate buffer pH 7.4.
Table 1 - Compound Extraction from Stainless Steel Mesh following 72 hrs Stirring in Phosphate Buffer, pH 7.4
= ea not etecte n u er souton

Claims

Claims
1. A method for storing and dispensing a compound, which comprises (1) adsorbing the compound onto a carrier having a metal surface (2) when later required removing the compound from the carrier by contacting liquid, in which the compound is soluble, with the surface of the compound containing carrier and (3) removing the liquid from the carrier.
2. A method as claimed in claim 1 wherein the metal surface is a mat made from a woven mesh of metal fibres, or metal coated non-metal fibres.
3. A method as claimed in claim 2 wherein several compounds are deposited upon zones of the same mat.
4. A method as claimed in claim 2 or claim 3 wherein the compound is removed from the mat by passing a volume of liquid known to dissolve the compound through the mat at the zone in which the compound is stored.
5. A method as claimed in claim 1 wherein the carrier having a metal surface is a fibre, wire, pin, rod, mesh, grid, powder sheet or strip.
6. A method as claimed in any preceding claim wherein the metal surface is steel, aluminium, chromium, silver or gold.
7. A method for storing and dispensing a number of different compounds with different physical properties which comprises (1) adsorbing each compound onto a carrier having a metal surface, (2) storing the adsorbed compounds on the metal surface until a compound is required, (3) extracting the compound from the carrier and (4) dispensing the compound.
8. A compound collection comprising a number of different compounds wherein each compound has been adsorbed onto a carrier having a metal surface.
9. A compound collection as claimed in claim 8 wherein the number of different compounds is more than 100.
EP00979766A 1999-12-02 2000-11-28 Inert carriers Withdrawn EP1242801A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9928368.1A GB9928368D0 (en) 1999-12-02 1999-12-02 Inert carriers
GB9928368 1999-12-02
PCT/GB2000/004531 WO2001040761A1 (en) 1999-12-02 2000-11-28 Inert carriers

Publications (1)

Publication Number Publication Date
EP1242801A1 true EP1242801A1 (en) 2002-09-25

Family

ID=10865492

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00979766A Withdrawn EP1242801A1 (en) 1999-12-02 2000-11-28 Inert carriers

Country Status (5)

Country Link
EP (1) EP1242801A1 (en)
JP (1) JP2003515609A (en)
AU (1) AU1715801A (en)
GB (1) GB9928368D0 (en)
WO (1) WO2001040761A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2763668A4 (en) * 2011-10-05 2015-04-15 Douglas Pharmaceuticals Ltd Pharmaceutical methods and topical compositions containing acitretin

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4588555A (en) * 1982-10-04 1986-05-13 Fmc Corporation Device for use in chemical reactions and analyses
US5519218A (en) * 1993-08-04 1996-05-21 Chang; On Kok Sample holder for spectroscopy
WO1996028248A1 (en) * 1995-03-15 1996-09-19 City Of Hope Disposable reagent storage and delivery cartridge
US5751629A (en) * 1995-04-25 1998-05-12 Irori Remotely programmable matrices with memories
DE19622628A1 (en) * 1996-06-05 1997-12-11 Boehringer Mannheim Gmbh Stabilization of metal conjugates
GB9816316D0 (en) * 1998-07-28 1998-09-23 Zeneca Ltd Compound storage

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0140761A1 *

Also Published As

Publication number Publication date
JP2003515609A (en) 2003-05-07
GB9928368D0 (en) 2000-01-26
WO2001040761A1 (en) 2001-06-07
AU1715801A (en) 2001-06-12

Similar Documents

Publication Publication Date Title
Valenzuela et al. A new carbon nanomaterial solid-phase microextraction to pre-concentrate and extract pesticides in environmental water
GB2370114A (en) Sample support plates for mass sprectroscopic analyses
US9034278B2 (en) Sample preparation for spectroscopy analysis
EP2805144A1 (en) Preparation of specimen arrays on an em grid
CN109682897B (en) Method for simultaneously determining multiple endocrine disruptors in environmental water sample
WO2001040761A1 (en) Inert carriers
US4377641A (en) Method and apparatus for the continuous extraction of ingredients from samples
Harrington et al. The use of high‐performance liquid chromatography for the speciation of organotin compounds
JP2023520563A (en) A method for measuring or identifying a component of interest in a sample
EP3477299B1 (en) Method for identification of high affinity complexes comprising two ligands and a receptor, device for carrying out said method and self-assembling chemical library for use in the method
Spitzer et al. Membrane filters as adsorbents for polynuclear aromatic hydrocarbons during high-volume sampling of air particulate matter
Nomizu et al. Electron microscopy of submicron particles in natural waters—specimen preparation by centrifugation
US5023452A (en) Method and apparatus for detecting trace contaminents
Li et al. Composite Material that Comprised Metal–Organic Nanotubes and a Sponge as a High‐Performance Adsorbent for the Extraction of Pharmaceuticals and Personal Care Products from Environmental Water Samples
Manouchehri et al. Study of trace metal partitioning between soil–EDTA extracts and Chelex-100 resin
WO1998016312A1 (en) Pipette
WO2001039877A1 (en) Inert carriers
Woodward et al. A field sampling method for obtaining representative samples of composite fluvial suspended sediment particles for SEM analysis
US10436682B2 (en) Sample preparation for spectroscopy analysis
Yabuki et al. Residual biomass of coffee as a binding agent in diffusive gradients in thin-films technique for Cd, Cu, Ni, Pb and Zn measurement in waters
Bağ et al. Determination of zinc, cadmium, cobalt and nikel by flame atomic absorption spectrometry after preconcentration by poly (ethylene terephthalate) fibers grafted with methacrylic acid
Pichon Multiresidue solid-phase extraction for trace-analysis of pesticides and their metabolites in environmental water
Emmenegger et al. Quantitative analysis of polycyclic aromatic hydrocarbons in water in the low-nanogram per liter range with two-step laser mass spectrometry
Rantala et al. Partition and determination of cadmium, copper, lead and zinc in marine suspended particulate matter
US6626982B1 (en) Compound storage

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20020702

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

17Q First examination report despatched

Effective date: 20080107

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20080520