WO2000040401A1 - Extraction material and method for determination of gamma-hydroxybutyrate - Google Patents
Extraction material and method for determination of gamma-hydroxybutyrate Download PDFInfo
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- WO2000040401A1 WO2000040401A1 PCT/US2000/000030 US0000030W WO0040401A1 WO 2000040401 A1 WO2000040401 A1 WO 2000040401A1 US 0000030 W US0000030 W US 0000030W WO 0040401 A1 WO0040401 A1 WO 0040401A1
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- 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
- B01J20/10—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
- B01J20/103—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate comprising silica
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- 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
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
- B01J20/28004—Sorbent size or size distribution, e.g. particle size
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- 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
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/282—Porous sorbents
- B01J20/283—Porous sorbents based on silica
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- 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
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
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- 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
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- 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
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
- B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
- B01J20/3257—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one of the heteroatoms nitrogen, oxygen or sulfur together with at least one silicon atom, these atoms not being part of the carrier as such
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- 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
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
- B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
- B01J20/3257—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one of the heteroatoms nitrogen, oxygen or sulfur together with at least one silicon atom, these atoms not being part of the carrier as such
- B01J20/3261—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one of the heteroatoms nitrogen, oxygen or sulfur together with at least one silicon atom, these atoms not being part of the carrier as such comprising a cyclic structure not containing any of the heteroatoms nitrogen, oxygen or sulfur, e.g. aromatic structures
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- 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
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/54—Sorbents specially adapted for analytical or investigative chromatography
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- 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
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/58—Use in a single column
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- 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
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/62—In a cartridge
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2991—Coated
- Y10T428/2993—Silicic or refractory material containing [e.g., tungsten oxide, glass, cement, etc.]
- Y10T428/2995—Silane, siloxane or silicone coating
Definitions
- the invention relates to a novel treated silica which is useful for analytical sample preparation by solid phase extraction, and to a method of use of this novel silica. More specifically, the invention relates to a silica treated with phenyltrichlorosilane and with 3-mercaptopropyltrimethoxysilane, to a solid phase extraction cartridge and an extraction column comprising the treated silica of the invention, and to a method of using the silica of the invention for sample preparation and analysis.
- the novel silica, column and method are all particularly well suited for use in the determination of gamma hydroxybutyric acid (GHB).
- Gamma hydroxybutyric acid also known as 4- hydroxybutyric acid and having the Chemical Abstracts Service Registry Number 591- 81-1, is a pharmaceutical which has been used for treatment of alcohol abuse and as a treatment for narcolepsy.
- GHB as used herein also refers to any salt form of gamma hydroxybutyric acid.
- GHB is also sometimes used as a drug of abuse.
- GHB has also been used recently as a "date rape drug", being used to render a victim disoriented or unconscious.
- the disclosure of the present invention is directed to a novel method for analysis of GHB in samples, and to a novel composition useful for solid phase extraction methods used in analytical chemistry.
- the treated silica is believed to be functionalized with both propylsulfonic acid groups and phenyl groups as a result of the treatment.
- Solid phase extraction is a method used for sample preparation in analytical chemistry.
- a solid sorbent material is used to contact a solution being analyzed.
- An analyte of interest may be bound reversibly and selectively by the sorbent material, thereby separating it from an interfering substance which may be present in the solution.
- the sorbent material may be used to selectively bind an interfering substance present in the solution, and thereby separate that substance from the analyte of interest which is left in the solution.
- the treated silica of the present invention may be used as a sorbent material in either of these ways to effect separations for use in analytical chemistry.
- Solid phase extraction methods are frequently carried out using a sorbent material which is carried within an extraction device such as a cartridge or a column.
- the extraction device is designed to be inexpensive to manufacture and therefore disposable after a single use.
- These extraction devices are generally tubular in shape, and sized to fit either a syringe or a vacuum manifold.
- the sorbent material used with such an extraction device is held in place within the cartridge or column by a frit selected for its ability to retain the sorbent material, while allowing a solvent to pass through the cartridge or column.
- the present invention encompasses both a cartridge extraction device and a column extraction device within its scope.
- GHB gamma hydroxybutyric acid (also known as 4-hydroxybutyric acid ) or a salt of gamma hydroxybutyrate (also known as 4-hydroxybutyrate), wherein the salt is an alkali metal salt
- GBL gamma butyrolactone
- BSTFA bis(trimethylsilyl)trifluoroacetamide - used as BSTFA/TMCS mixture
- TMS trimethylsilyl
- UV ultraviolet VIS — visible
- the free acid or salt form of GHB is a scheduled drug, that is a drug whose possession is regulated by the United States Drug Enforcement Administration.
- a method for determining GHB in samples such as biological samples or body fluids, which method would be definitive. That is, the method should measure GHB present in the sample which is present as either the free acid or salt, but whose results would not be affected by the presence of gamma butyrolactone in the same sample.
- the method should be one which can provide definitive proof of the presence of the controlled substance form of GHB in a sample. The results determined with such a method would be of great value to law enforcement officials for providing evidence of illicit drug use.
- the lactone GBL is not a controlled substance, it is highly desirable to have an analytical method for GHB which can determine GHB quantitatively without interference from GBL.
- having GHB in a subject's urine is evidence of the commission of a crime while having GBL in the subject's urine may not be a crime.
- forensic and clinical laboratories analyze for GHB by extracting GHB from urine samples by conversion to GBL by acidification, followed by extraction into either chloroform or ether, and then using capillary GC analysis with either flame ionization detection or mass spectrometry to quantitate GBL. This method does not directly measure GHB however, but rather the lactone. This method then is not a definitive test for GHB, but instead measures GHB as well as any GBL in a sample.
- GHB is not a scheduled drug, this will not provide firm scientific evidence needed in court to obtain a conviction on drug charges.
- a definitive test for GHB which would measure the free acid or salt in a sample, and which can distinguish GHB from the lactone GBL, would be of value to forensic laboratories.
- a method for determination of GHB should also be useful for analysis of GHB from samples other than biological samples as well. Examples of these other samples include but are not limited to oils, extracts, elixirs and beverages which might contain GHB; and which are suspected as being intended for illicit administration to people.
- the short half life of GHB after administration to a subject is also a problem for detection of the drug.
- the half life is reported to be less than one hour. Peak urine concentrations after ingestion are observed at about 4 hours. No drug is detected after 12 hours from ingestion. Less than 5% of an oral dose is excreted in urine as the unchanged drug (S. D. Ferrara et al., Therapeutic gamma-hydroxybutyric acid monitoring in plasma and urine by gas chromatography-mass spectroscopy, Journal of Pharmacology and Biomedical Analysis, 11:6, 483-487, 1993).
- an analytical method for determination of GHB to be of practical use it must be suited for rapid use when a sample suspected to contain GHB becomes available.
- GHB are limited. GHB has been reported to have very low absorption in the ultraviolet region. Because of this, HPLC analysis would require refractive index detection. This would clearly not provide a very sensitive detection method, and would present a serious problem with respect to obtaining sufficient resolution from interfering substances. The use of capillary electrophoresis would be faced with the same limitations of detection.
- Derivatization of GHB would be required to introduce a chromophore into GHB which would allow more sensitive detection using separation methods such as HPLC or capillary electrophoresis.
- GHB is not readily determined by gas chromatography (GC). At temperatures above about 140°C, GHB is converted to gamma butyrolactone (GBL) in an injection port. This indicates that derivatization such as silylation would be desirable to prevent formation of the lactone and adds to volatility of GHB prior to injection onto a GC column. Coupling of separation by gas chromatography with mass spectroscopic determination of the separated analytes is a problem with GHB because the mass spectra for GHB and the lactone GBL have been reported to be nearly identical. This problem has been discussed in Kathleen Andrews, Getting the Scoop on GHB: The New Adventureal Drug, Workshop at 49th Annual Meeting of the American Academy of Forensic Sciences, February 17-22, 1997.
- This reported method comprises the steps: a) adding the internal standard to a sample; b) adding a quantity of sulfuric acid for acidification; c) centrifuging the sample; d) decanting the supernatant; e) adjusting the pH to between 6 and 7; f) centrifuging again; g) adding n-butyl chloride to the supernatant; h) centrifuging again; i) removing the solvent layer; j) reducing the solvent volume by evaporation; and k) submitting a sample of the solvent layer to gas chromatography on a capillary column with flame ionization detection.
- GHB Gamma- Hydroxybutyrate
- GBL Gamma-Butyrolactone
- GHB suitable for illicit sale would be expected to have a high concentration of GHB, although some inactive diluent might also be present.
- concentration in an illegal preparation for sale would certainly be much higher than would be expected for a sample taken from a subject suspected to have ingested GHB.
- GHB may be determined quantitatively by use of isotope dilution with deuterated GHB being used.
- the analyte being determined was the butyrolactone, GBL. That is, GHB in a sample was converted in the method of Gibson to GBL by acidification. GBL was then separated on a silicic acid column from other substances present in the sample.
- GBL eluted from the silicic acid column was trimethylsilylated for further separation and quantitation by GC-MS.
- Deuterated GBL D6-butyrolactone
- This method suffers from the disadvantage that GHB is not directly determined. That is, the method of Gibson is not definitive for GHB.
- a sample is acidified for conversion of any GHB in the sample to GBL. This step allows the use of D6-GBL as a stable isotope dilution internal standard to allow for any sample loss which might occur during the steps of the method.
- the method of Gibson then performs a separation of GBL by chromatography on silicic acid.
- a sample which might originally contain the lactone, GBL, but no GHB; would give a result similar to that which would be obtained for a sample which would originally contain an equivalent amount of GHB and no lactone. Therefore, the method disclosed by Gibson is not definitive for GHB, and might not provide suitable scientific evidence for supporting criminal charges of illicit use of GHB.
- the invention comprises a novel extraction material composition for use in solid phase extraction of an analyte from a solution, the material comprising silica which has been treated with phenyltrichlorosilane and with 3- mercaptopropyltrimethoxysilane.
- This treated silica is presumed to carry both propylsulfonic acid groups and phenyl groups.
- the composition of the invention comprises a silica which has been chemically treated to have both propylsulfonic acid functional groups and phenyl functional groups, and which is of a particle size which makes the silica composition useful as a sorbent for analytical sample preparation.
- the composition of the present invention preferably has the ability to retain sufficient interfering substances from a solution containing GHB to allow quantitative measurement of the GHB content of the solution.
- the invention also comprises a method for solid phase extraction using the novel composition. More particularly, the invention comprises a method for quantitative determination of gamma hydroxybutyric acid and gamma hydroxybutyrate in samples which may contain interfering substances of biological origin, and may also contain gamma butyrolactone.
- the invention also encompasses an extraction cartridge containing the novel derivatized silica composition described herein.
- the extraction cartridge is useful for carrying out solid phase extraction of analytical samples.
- the extraction cartridge encompassed may have a tubular form, may be disk shaped or have some other shape.
- the invention also includes an extraction column for solid phase extraction of analytical samples.
- the method of the invention involves separation of GHB from a sample for analysis.
- the sample may be a composition which is suspected of containing GHB in concentrated form in solution.
- An example of such a composition is a sample taken from suspected drug dealer.
- the sample may be a biological sample, such as a quantity of urine, serum, or whole blood which is suspected of containing GHB.
- the method of the invention uses a silica composition treated according to the invention to separate interfering substances from GHB in a sample. This method results in a purification of GHB from interfering substances which is sufficient to allow GHB to be determined quantitatively.
- the new treated silica, extraction devices and method allow purification of GHB from interfering substances frequently present in biological samples sufficiently to make subsequent analysis by chromatography more effective than in currently available methods.
- silica of the present invention is a novel composition having received two treatments with silane reagents. It is believed that the inventive silica has a novel capability to bind substances.
- treated silica which provides unique properties useful for solid phase extraction in analytical chemistry. While the treated silica according to the present invention has other uses, it is particularly well suited for use in solid phase extraction and particularly well suited for solid phase extraction used in GHB analysis.
- the unique properties of the inventive treated silica is a result of two treatments.
- One treatment is achieved by contacting silica with phenyltrichlorosilane.
- the other treatment is achieved by contacting the silica with 3-mercaptopropyltrimethoxysilane, followed by contacting the resulting silica with water.
- Treating a silica with both of these treatments leads su ⁇ risingly to a novel treated silica having an ability to purify analytes by solid phase extraction which is unique and previously unreported for any silica.
- Use of either treatment alone does not result in a silica with the unique and new properties of the inventive silica, and the ability to purify GHB by solid phase extraction.
- the novel method for GHB comprises solid phase extraction of a sample solution where interfering substances are retained sufficiently by the novel treated silica to allow any GHB present to be analyzed.
- the novel treated silica can be better used in solid phase extraction techniques when used in the form of an extraction cartridge or an extraction column, and the present invention encompasses such devices containing the treated silica. These extraction cartidges or columns are generally tubular in shape or sometimes disk shaped.
- the novel silica can also be supplied to a user in the form of a test kit which would contain a quantity of the new silica sorbent, and which might also contain other needed materials such as a chromatographic separation column, standards and a method of separation.
- the inventive treated silica may be of particle sizes from about 5 to about 300 ⁇ m. It is preferred that the silica be of particle sizes from about 30 to about 80 ⁇ m, and it is most preferred that the silica be of from about 40 to about 63 ⁇ m in size.
- the treated silica is made by treating an amo ⁇ hous silica. It is also preferred that the silica to be treated is porous. However, other types of silica can also be used in practicing the invention, such as a nonporous or a pellicular silica.
- the treated silica disclosed here can be used effectively as a solid phase sorbent in the analysis of many drugs other than GHB.
- drugs which have been quantified using the novel silica include: acetopromazine, acetaminophen, amantadine, arnitriptyline, amphetamine, apomo ⁇ hine, azaperone, barbiturates, benzocaine, benzoic acid, benzoylecgonine, benztropine, buspirone, caffeine, carbamazepine, carisoprodol, chlordiazepoxide, chloroquine, chlo ⁇ heniramine, chlo ⁇ romazine, chlo ⁇ ropamide, clenbuterol, clonazepam, cocaine, codeine, cotinine, cresol, cyclobenzaprine, dextrometho ⁇ han, dextrophan, diazepam, dihydrocodeine, diltiazem,
- the new treated silica can also be used effectively in the analytical determination of drug metabolites.
- Examples of metabolites which have been successfully determined using this silica include: azaperone-5-glucuronide, et ⁇ hine-3-glucuronide, mo ⁇ hine-3- glucuronide, and nal ⁇ hine-3-glucuronide.
- a silica composition in accordance with the invention was produced by treating a silica by a method comprising the following steps.
- the silica used was an amo ⁇ hous form of silica, comprising irregular particles having a particle size distribution of from about 40 to about 63 ⁇ m, and having a mean porosity of about 6.0 nm.
- the silica was reacted with phenyltrichlorosilane in a mixture of methylene chloride and water, the silane being slowly added to a suspension of the silica in the solvents.
- the reaction mixture was then washed with methanol (5 liters per kilogram).
- the reacted silica was then treated with water at 80°C by suspending the silica in water, at 1.5 liters of water to 1 kg of silica. The reacted silica was then washed with 3 liters of water. The silica was then washed with 3 liters of room temperature water until the eluant was at pH of 4.5. The silica was then washed with 2 liters of methanol. Then, the silica was dried under vacuum at 70 °C and about 508 torr. The treated silica was then suspended in methylene chloride and glacial acetic acid. To the suspension was added slowly 3- mercaptopropyltrimethoxysilane.
- the silica was then separated from the suspension solvent solution by filtration, and then washed with 1 liter of methanol followed by two washes with 2 liters of methanol.
- Hydrolysis of the mercapto group to a sulfonic acid was carried out by adding to the silica hot aqueous 4.2 percent hydrogen peroxide, using 1.5 liters of 4.2% hydrogen peroxide at 80°C, followed by 1.5 liters of 4.2 percent hydrogen peroxide, and allowing the resulting silica to stand for 30 minutes.
- a second hydrolysis was then carried out by addition of 1.5 liters of purified water at 80°C to suspend the silica, followed by suspending in 3 liters of water to hydrolyze the silica.
- a method for analysis in accordance with the invention was carried out by performing the following steps.
- the analyte determined in this example was GHB.
- a solid phase extraction column according to the invention was conditioned in a vacuum manifold with 3 mL of methanol, 3 mL of distilled water and 1 rnL of 0.1 M phosphate buffer at pH 6.0 in turn.
- Selected ion monitoring was used for three ions for each analyte. The dwell times were set to 50 milliseconds per ion.
- the most prevalent ions for GHB- diTMS are 147, 233, 148, 149, 204, 143, and 234 m/z.
- the most prevalent ions for GHB- D6-diTMS are 147, 239, 148, 149, 206, and 240 m/z.
- Urea was also derivatized by BSTFA to form a TMS derivative.
- the trimethylsilylated product from urea elutes near GHB-diTMS and has many of the same ions, including 147, 148 and 149; therefore some of the less abundant ions must be used for the SLM analysis. These include those shown as follows:
- Samples of urine were analyzed for GHB by the following procedure. This procedure differed from that in Example 2 primarily by further including a step wherein urease was added to the samples to break down urea present in the samples. a) lOO ⁇ L of GHB-D6 solution were added (100 ng/ ⁇ L) to each sample in 13 x 100 mm culture tubes.
- Extraction columns containing a silica according to the invention were conditioned by washing each column with 3 mL of methanol, followed by 3 mL deionized water, and then 1 mL of 0.1 M phosphate pH 6.0 buffer on a vacuum manifold.
Abstract
Description
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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CA002326399A CA2326399A1 (en) | 1999-01-04 | 2000-01-03 | Extraction material and method for determination of gamma-hydroxybutyrate |
EP00901380A EP1082214A1 (en) | 1999-01-04 | 2000-01-03 | Extraction material and method for determination of gamma-hydroxybutyrate |
AU22229/00A AU2222900A (en) | 1999-01-04 | 2000-01-03 | Extraction material and method for determination of gamma-hydroxybutyrate |
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US09/224,691 | 1999-01-04 | ||
US09/224,691 US6156431A (en) | 1999-01-04 | 1999-01-04 | Extraction material comprising treated silica and method for determination of gamma-hydroxybutyrate |
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WO2000040401A1 true WO2000040401A1 (en) | 2000-07-13 |
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PCT/US2000/000030 WO2000040401A1 (en) | 1999-01-04 | 2000-01-03 | Extraction material and method for determination of gamma-hydroxybutyrate |
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US (1) | US6156431A (en) |
EP (1) | EP1082214A1 (en) |
AU (1) | AU2222900A (en) |
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US6592782B2 (en) * | 1993-12-08 | 2003-07-15 | Eltron Research, Inc. | Materials and methods for the separation of oxygen from air |
US6703216B2 (en) | 2002-03-14 | 2004-03-09 | The Regents Of The University Of California | Methods, compositions and apparatuses for detection of gamma-hydroxybutyric acid (GHB) |
US7238533B1 (en) | 2003-07-22 | 2007-07-03 | Ronald Legge | Personal illicit drug detection method |
US7914766B1 (en) * | 2004-06-03 | 2011-03-29 | Ut-Battelle Llc | Inorganic resins for clinical use of 213Bi generators |
US8920857B2 (en) | 2010-12-22 | 2014-12-30 | Michael T. Abramson | System and method for detection of a contaminated beverage |
US9285352B2 (en) | 2010-12-22 | 2016-03-15 | Drinksavvy, Inc. | System and method for detection of a contaminated beverage |
CN103962114B (en) * | 2014-05-22 | 2015-11-11 | 武汉大学 | The preparation method of electroconductive polymer coating silica gel and the application in SPE thereof |
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US5955377A (en) * | 1991-02-11 | 1999-09-21 | Biostar, Inc. | Methods and kits for the amplification of thin film based assays |
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ATE15378T1 (en) * | 1980-06-27 | 1985-09-15 | Akzo Nv | POROUS, INORGANIC SUPPORT MATERIAL COVERED WITH A FIXED ORGANIC PHASE, APPLICATION FOR CHROMATOGRAPHY AND ITS PRODUCTION PROCESS. |
US4724207A (en) * | 1984-02-02 | 1988-02-09 | Cuno Incorporated | Modified siliceous chromatographic supports |
US4640909A (en) * | 1985-05-07 | 1987-02-03 | J. T. Baker Chemical Company | Bonded phase of silica and carboalkoxyalkyl silanes for solid phase extraction |
US4680120A (en) * | 1985-05-07 | 1987-07-14 | J. T. Baker Chemical Company | Bonded phase of silica and carboalkoxyalkyl silanes for solid phase extraction |
US4950634A (en) * | 1988-02-11 | 1990-08-21 | Dow Corning Corporation | Method for producing dual zone materials by use of an organosilane mixture |
JPH0678347B2 (en) * | 1989-01-13 | 1994-10-05 | 信越化学工業株式会社 | Organic silicon compound |
US5137626A (en) * | 1989-02-21 | 1992-08-11 | Rohm And Haas Company | Solid-phase extraction tubes containing sulfonazide bonded-phase extractants |
US5011410A (en) * | 1989-09-14 | 1991-04-30 | Minnesota Mining And Manufacturing Co. | Silane-treated metal dental articles |
US5831073A (en) * | 1990-10-31 | 1998-11-03 | The Research Foundation Of State University Of New York | Ion triggered alkylation of biological targets by silyloxy aromatic agents |
US5512169A (en) * | 1992-12-30 | 1996-04-30 | Dow Corning Corporation | Liquid column packing materials |
DE4403940A1 (en) * | 1994-02-08 | 1995-08-10 | Genomed Molekularbiologische U | Chromatography material |
US5824226A (en) * | 1994-12-21 | 1998-10-20 | Loyola University Of Chicago | Silane-modified clay |
JP3222386B2 (en) * | 1996-07-12 | 2001-10-29 | 信越化学工業株式会社 | Coating composition and article treated with the coating composition |
-
1999
- 1999-01-04 US US09/224,691 patent/US6156431A/en not_active Expired - Lifetime
-
2000
- 2000-01-03 WO PCT/US2000/000030 patent/WO2000040401A1/en not_active Application Discontinuation
- 2000-01-03 AU AU22229/00A patent/AU2222900A/en not_active Abandoned
- 2000-01-03 EP EP00901380A patent/EP1082214A1/en not_active Withdrawn
- 2000-01-03 CA CA002326399A patent/CA2326399A1/en not_active Abandoned
Patent Citations (2)
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US5955377A (en) * | 1991-02-11 | 1999-09-21 | Biostar, Inc. | Methods and kits for the amplification of thin film based assays |
US5948231A (en) * | 1995-04-20 | 1999-09-07 | Perseptive Biosystems, Inc. | Compositions, methods and apparatus for ultrafast electroseparation analysis |
Also Published As
Publication number | Publication date |
---|---|
AU2222900A (en) | 2000-07-24 |
EP1082214A1 (en) | 2001-03-14 |
US6156431A (en) | 2000-12-05 |
CA2326399A1 (en) | 2000-07-13 |
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