EP1664728A1 - Detection d'analytes dans une zone definie du corps - Google Patents

Detection d'analytes dans une zone definie du corps

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Publication number
EP1664728A1
EP1664728A1 EP04763355A EP04763355A EP1664728A1 EP 1664728 A1 EP1664728 A1 EP 1664728A1 EP 04763355 A EP04763355 A EP 04763355A EP 04763355 A EP04763355 A EP 04763355A EP 1664728 A1 EP1664728 A1 EP 1664728A1
Authority
EP
European Patent Office
Prior art keywords
adsorbent
adsorbent material
analyte
compounds
odor
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Withdrawn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
EP04763355A
Other languages
German (de)
English (en)
Inventor
Andrea Büttner
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Priority to EP04763355A priority Critical patent/EP1664728A1/fr
Publication of EP1664728A1 publication Critical patent/EP1664728A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/0064—Devices for taking samples of body liquids for taking sweat or sebum samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/405—Concentrating samples by adsorption or absorption
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N2001/028—Sampling from a surface, swabbing, vaporising

Definitions

  • the invention relates to a method for determining qualitatively or quantitatively one or more analytes present in a defined area of the body of a subject; an adsorbent article or a patch suitable to be applied in this method and the use of the adsorbent article or the patch for determining qualitatively or quantitatively one or more analytes.
  • the intensity and duration of perception of odor compounds during and after food consumption is influenced by a complex series of physiological and physical- chemical processes.
  • two key modes have to be distinguished, a) the immediate aroma impression when food is present in the oral cavity or is just swallowed and b) the prolonged retronasal aroma perception after swallowing, often called aftertaste or better "afterodor” or “aftersmeH” when talking of odorants.
  • aftertaste or better "afterodor” or "aftersmeH” when talking of odorants.
  • Odorous substances are found amongst very different substance classes such as esters, aldehydes, alcohols, thio-compounds, heteroaromatic or terpenic compounds and many more.
  • Prolonged retronasal aroma perception as it is perceived after complete swallowing of a food, must be induced by persistent odorants which are present in the oral cavity during a certain period. This means that they are adsorbed to oral mucosa as a kind of aroma reservoir and released therefrom continuously.
  • This adsorption of odorants as it has been previously shown to occur (1 , 2), can be regarded as the only possible explanation for the persistence of odorous molecules after food consumption and for the development and/or duration of the so-called afterodor. Up to now, the premises for this phenomenon could not be fully elucidated. As discussed above, it has been shown that odorants are adsorbed to the oral mucosa.
  • salivary enzymes As another aspect of the phenomenon, the influence of human salivary enzymes on the differences in persistence between odorants, apart from physicochemical parameters such as polarity and volatility, has been proposed (3, 4).
  • saliva can act as an aroma extraction and transporting system by continuously extracting odorants from materials which are not swallowed, for example chewing gum. These compounds are then transferred during the swallowing process into the pharyngeal areas where they can be perceived retronasally as described in (1).
  • the same extraction process that means a kind of "washing-out" effect, has been assumed for , odorants which are adsorbed to the oral mucosa.
  • the main goal of the present study was to develop a technique which allows the characterization of potent odorants released into the oral cavity even at extremely low concentrations from the oral mucosa or from films covering the mucosa like a kind of coating.
  • SBSE stir bar sorptive extraction
  • a PDMS-coated stir bar is exposed for a certain extraction time to a certain volume of sample either with or without preliminary application of derivatization techniques.
  • the analytes can be easily recovered via extraction or thermodesorption and analysed e.g. by gaschromatography or liquid chromatography in combination with the respective detector systems.
  • the SBSE has several advantages such as convenient handling, high extraction capacity, very low amounts of PDMS breakdown products and many more (6).
  • the invention relates to a method for determining qualitatively or quantitatively one or more analytes present in a defined area of the body of a subject characterised by the following steps: a) applying an adsorbent material to the defined area of the body of a subject, b) extracting the analyte from said area and removing the adsorbent material from the defined area of the body, c) desorbing the analyte from the adsorbent material, and d) detecting the analyte qualitatively or quantitatively.
  • steps a-d) are repeated at least once.
  • the area of the body is the oral cavity, the nasal cavity, the vagina, the anal cavity, hair, or another area of the skin.
  • the invention further relates to a method where the area of the body is selected from mouth, nose, vagina, anal cavity, hair, especially head hair, or areas of the skin, including armpits .
  • the following steps are conducted: a) applying an adsorbent article to the defined area of the body from a living subject at predefined starting point b) extracting the analyte for a defined period from said area and removing the adsorbent article from the defined area of the body c) desorption of the analyte from the adsorbing material d) detection of the analyte e) optionally steps a-d) are carried out more than once where optionally the extraction period in b) may vary.
  • the invention further relates to a method as defined above where a composition comprising the analytes or a precursor thereof is administered to a subject prior to application of the adsorbent material.
  • steps a-d) or all steps may be carried out more than once and the interval between administration of the composition and starting point a) may vary between every analyses.
  • composition comprising the analytes or a precursor thereof is administered to orally.
  • the invention relates to a method as defined above where the adsorbent material or article is introduced into the mouth and extraction takes place within the mouth.
  • composition is selected from food, beverage, or a matrix spiked with the analyte or a precursor, tobacco-ware or the smoke thereof.
  • the component comprising the analytes or a precursor thereof is administered topically.
  • the composition is selected from fragrances, deodorants, antiperspirants, skin care products, cleansing products, decorative cosmetic products, pharmaceutically active topical preparations, and mixtures thereof; more preferably the composition is formulated as a medicament or cosmetic, perfume, skin care, hair-wash, deodorant, ointment, cream, sun cream, lotion, soap, shampoo, or other rinsing product.
  • the invention furthermore relates to a method as defined above where the composition comprising the analytes or a precursor thereof is administered topically , and the adsorbent material is applied to the skin and extraction takes place at the surface of the skin.
  • Application of the adsorbent article may take place at an area different to where the administration of said composition took place or at the same area. In most cases the latter option is preferred.
  • the composition comprising the analyte or a precursor thereof is administered nasally, anally, or vaginally.
  • the adsorbent material is applied to the nasal cavity, vagina, or anal cavity, respectively, and extraction takes place at the nasal cavity, vagina or anal cavity, respectively.
  • the adsorbent material is selected from compounds of polydialkylsiloxanes, polyphenyleneoxides, divinylbenzene, polyacrylates, activated alumina, carbon black, carbon molecular sieve adsorbent resins, polyethylene glycols, diatomaceous earth based adsorbents and mixtures of two or more thereof.
  • polydialkylsiloxanes polyphenyleneoxide (Tenax ®), divinylbenzene, carbowax/ divinylbenzene, carboxen/PDMS, PDMS/divinylbenzene, carboxen/divinylbenzene, and polyacrylate.
  • Polydialkylsiloxanes such as polydimethylsiloxane (PDMS), divinylbenzene, carbowax /divenylbenzene, carboxen/PDMS, PDMS/divenylbenzene, carboxen/divinylbenzene, polyacrylate are particularly preferred.
  • the most preferred adsorbent material is PDMS.
  • the adsorbent article is a fiber or a stir bar coated with an above adsorbent material.
  • the preferred adsorbent article is a stir bar coated with PDMS or PDMS without support such as a film made of PDMS.
  • analyte is selected from one or more of the following: - pharmaceutically active compounds, - cosmetically active compounds, - toxic compounds, - pheromones or hormones, - proteins, carbohydrates or fats present in food, - flavours, - compounds inducing a physical perception, or a degradation product of the above.
  • flavours are selected from compounds inducing a chemoreception and compounds inducing a trigeminal perception.
  • compounds inducing a physical perception are selected from compounds inducing a haptic perception, compounds eliciting a sensation selected from temperature, pain, astringency, and mouth feel.
  • the analyte is selected from proteins, carbohydrates, fats, tastants or other compounds inducing any kind of chemo- or physio-perception, types of compounds eliciting a trigeminal sensation in the in the nasal, oral or pharyngeal area, volatiles and odours.
  • the analyte is selected from a volatile, tastant, odorants or a degradation product thereof.
  • the analyte is an odorant.
  • desorption is made by thermal desorption.
  • detection is performed by GC, preferably by GC/MS, GC/Olfactometry or GC/MS/Olfactometr .
  • HRGC/O high resolution gas chromatography
  • the period of extracting the analyte from the defined area of the body ranges from 1 min to 24 h, preferably from 1 min to 1 h.
  • the period of extracting is preferably from 1-10 min, more preferably from 2-5 min, more preferably from 4-5 minutes and preferred 5 min.
  • the period of extracting is preferably from 1 min to 5 h, more preferably from 10 min to 2 h, preferred from 10 min to 1 h, most preferred 30 min.
  • composition comprising the analytes or a precursor thereof is administered prior to extraction the starting point for the application of the adsorbent article and the area of the body ranges from 15 sec to 2 days after administration of the composition.
  • the starting point for the application of the adsorbent article preferably ranges from 15 sec to 25 min, preferably from 1 min to 20 min, preferred from 1 min to 5 min, after elimination of the composition from the mouth. If extraction takes place at the skin the starting point for the application of the adsorbent article preferably ranges from 2 min to 48 h, preferably from 1 h to 12 h after administration of the composition.
  • the method comprises the following steps: a) oral administration of a composition comprising the odorants or precursors thereof, where the composition is selected from food, a matrix spiked with odorants or a beverage, or tobacco-ware to a subject b) contacting an adsorbent with the saliva from said subject at predefined starting point, where the adsorbent material preferably is PDMS c) extracting the analyte for defined period from said saliva d) thermal desorption of the analyte from the adsorbing material e) detection of the analyte by GC/MS, GC/Olfactometry , GC/MS/OIfactometry, Most preferred is high resolution gas chromatography (HRGC/O) f) steps a-e) carried out more than once where the starting points in b) differ from at least 15 sec and the extraction period in c) does not vary.
  • HRGC/O high resolution gas chromatography
  • the method comprises the following steps: a) oral administration of a composition comprising the odorants or precursors thereof, where the composition is selected from food, a matrix spiked with odorants or a beverage, a mouthwash or tobacco-ware to a subject b) contacting an adsorbent with the saliva from said subject at predefined starting point, point selected from 15 sec to 5 min, preferred from 15 sec to 2 min after elimination of the composition from the mouth where the adsorbent article is a stir bar coated with PDMS or a film made of PDMS.
  • the method comprises the following steps: a) oral administration of a composition comprising the odorants or precursors thereof, where the composition is selected from food, a matrix spiked with odorants, a beverage, a tobacco-ware or toothpaste to a subject b) introducing an adsorbent into the mouth of said subject at predefined starting point, where the adsorbent material preferably is PDMS c) extracting the analyte for defined period from the saliva, removing the adsorbent article from the mouth d) thermal desorption of the analyte from the adsorbing material e) detection of the analyte by GC/MS , GC/Olfactometry , GC/MS/OIfactometry, Most preferred is high resolution gas chromatography (HRGC/O) f) steps a-e) carried out more than once where the starting points in b) differ from at least 15 sec and the extraction period in c) does not vary.
  • HRGC/O high resolution gas chromatography
  • a further embodiment comprises the previous method where the starting point is selected from 15 sec - 5 min, preferred from 15 sec -to 2 min after elimination of the composition from the mouth.
  • a further embodiment comprises the previous methods where the adsorbent article is kept for 5 min within the mouth.
  • the method comprises the following steps: a) oral administration of a composition comprising the odorants or precursors thereof, where the composition is selected from food, a matrix spiked with odorants, or a beverage, a mouthwash, or tobacco-ware to a subject b) introducing an adsorbent article, preferably a stir bar coated with PDMS, or film made of PDMS, into the mouth of said subject at predefined starting points selected from 15 " sec-15 min, preferably from 15 sec to 5 min, and more preferred from 15 sec to 2 min, after elimination of said composition c) extracting the analyte for 5 min from said saliva in the mouth d) thermal desorption of the analyte from the adsorbing material e) detection of the analyte by HRGC/O f) steps a-e) carried out more than once where the starting points in b) differ from at least 15 sec and the extraction period in c) does not vary.
  • an adsorbent article preferably a stir bar coated with
  • the method comprises the following steps: a) topical administration of a composition comprising the odorants or precursors thereof, where the composition is selected from a medicament or cosmetic, perfume, skin care, hair-wash, deodorant, ointment, cream, sun cream, lotion, soap, shampoo, or other rinsing product.
  • adsorbent material preferably is PDMS c) extracting the analyte for defined period from the skin or the headspace of that area, removing the adsorbent article from the skin d) thermal desorption of the analyte from the adsorbing material e) detection of the analyte by GC/MS , GC/Olfactometry , GC/MS/OIfactometry, Most preferred is high resolution gas chromatography (HRGC/O) f) steps a-e) carried out more than once where the starting points in b) differ from at least 5 min and the extraction period in c) does not vary.
  • HRGC/O high resolution gas chromatography
  • a further embodiment comprises the previous method where the starting point is selected from 1 h to 12 h after application of the composition to the skin.
  • a further embodiment relates to the methods as mentioned above where the defined area of the skin are the armpits.
  • the present invention also provides an adsorbent article suitable to be applied in the above method comprising: a housing having at least three of apertures located in a manner that they allow a free flow of a fluid into and out of the housing, an adsorbent material included within this housing.
  • the adsorbent article comprises a porous capsule and an adsorbent material included therein.
  • the housing is made of metal, glass, silicone, plastic, ceramics or porcelain.
  • the capsule is made of glass and is suitable to be introduced into the mouth.
  • no further liquid-absorbing material is added to the adsorbent material.
  • the weight increase of the adsorbent material when exposed to a liquid is 0 to 5 weight % (20°C, 10 min).
  • the adsorbent material allows a thermal desorption of an analyte from same.
  • the adsorbent material allows an adsorption of an analyte by means of physiosorption.
  • the housing has the form of a tube which has apertures distributed over the tube. More preferably, the tube is releasably closed at both ends. In another embodiment, the housing has at least one flat surface with apertures distributed over said surface. In one embodiment, the housing is disposable.
  • the invention further relates to an adsorbent article included in a porous capsule.
  • the capsule may be made of glass and suitable to be introduced into the mouth.
  • the adsorbent material is made from PDMS.
  • the absorbent article is a stir bar, preferably coated with PDMS.
  • the adsorbent article is a film made of PDMS.
  • the capsule measures 15 mm or 25 mm in length.
  • the present invention further relates to a patch comprising a layer of an adsorbent material and a support provided on said adsorbent material.
  • the patch is designed in a manner that the adsorbent material such as a film of can be applied to the skin.
  • the support comprises a backing layer having provided thereon a layer of an adhesive.
  • the layer of an adhesive might be present as discontinuous or as continuous layer.
  • the adsorbent material can be easily removed from the patch.
  • the adsorbent material might be attached to the backing layer via the adhesive layer.
  • the absorbent material is fixed to the patch, only a small part of it should be fixed, but not with more than 40 % of the surface of the absorbent article.
  • 5 to 40% of the surface of the adsorbent material is attached to the backing layer.
  • the adsorbent material is not fixed to the patch.
  • the adsorbent material preferably is PDMS.
  • the present invention also relates to the use of an adsorbent article for determining qualitatively or quantitatively one or more analytes.
  • the use is in solid phase extraction.
  • the use is in the above method.
  • the present invention further relates to the use of a patch for determining qualitatively or quantitatively one or more analytes.
  • the use is in the above method.
  • the present invention is further directed to the use of the above method for selecting relevant compounds for the manufacture of a composition to be administered to a subject.
  • the invention is directed in on aspect to the use of compounds which have been determined to be relevant according to the above method for the manufacture of a composition to be administered to a subject.
  • the invention further relates to a method for determining qualitatively or quantitatively one or more analytes present at the surface of the skin after topical administration of a composition to a subject characterised by the following steps: a) topical administration of a composition comprising the analytes or a precursor thereof to defined area of the skin of a subject b) contacting an adsorbent article with the defined area of the skin from said subject at predefined starting point, where the adsorbent article preferably is a stir bar coated with adsorbent material, such PDMS, or a film made of PDMS c) extracting the analyte for defined period from area of the skin d) desorption of the analyte from the adsorbing material e) detection of the analyte f) optionally steps a-e) or b-e) are carried out more than once where the starting point in b) differs and optionally the extraction period in c) may vary.
  • the invention further relates to said method
  • the invention further relates to said method where the defined starting point is from 0 sec to 48 h, preferably from 1 min to 24 h, and more preferred from 5 min to 12 h.
  • subject means human being or animal.
  • the term includes men and women , independently from their age.
  • the method in accordance with the present invention is non-invasive, which means that it does not include a surgical treatment. Specifically, there is no physical impact on the defined area of the body.
  • adsorbent article means an article comprising an adsorbent.
  • adsorbent as used herein means an area where a substance to be assayed is immobilised.
  • immobilisation refers to attachment or entrapment, either chemically or otherwise, of material to another entity (e.g. a solid support, substrate, or surface) in a manner that restricts the movement of the material .
  • the adsorbent material must be suitable to adsorb the analyte.
  • the term adsorbent article includes articles which only consists of adsorbent material
  • the adsorbent material may be incorporated, enclosed or coated to a support.
  • support means any material that provides solid or semisolid structure with which another material can be incorporated, enclosed or coated. Such materials include smooth supports (e.g. metal, glass, plastic, silicon, ceramics) as well as textured and porous materials.
  • Such materials also include, but are not limited to, gels, rubbers, polymers, and other non rigid materials.
  • Preferred adsorbent articles are fibers or stir bars as commonly used in solid-phase microextraction (SPME) or stir bar sorptive extraction (SBSE).
  • SPME solid-phase microextraction
  • SBSE stir bar sorptive extraction
  • a film made of PDMS may be preferred.
  • the adsorbent material is selected from the above materials, more preferably polydialkylsiloxanes such as polydimethylsiloxane (PDMS), divinylbenzene, carbowax /divinylbenzene, carboxen/PDMS, PDMS/divinylbenzene, carboxen/divinylbenzene, polyacrylate.
  • the preferred adsorbent material is PDMS.
  • the preferred adsorbent article is a stir bar, comprising a first and innermost part which is a magnetic rod, a second part which is a thin glass jacket covering the magnetic stirring rod and a third outermost part which is a adsorbent layer of PDMS.
  • Such an article is commercially available from Gerstel GmbH , Germany called Twister ® .
  • the material used For use in the oral cavity the material used must be physiologically acceptable and must not be toxic, as proved for PDMS within the present invention.
  • the size and shape of the adsorptive article as well as surface area or coating thickness of the adsorptive layer may adapted to the needs.
  • the adsorptive article may be described by a thickness A, mm, a width B mm, and a length C mm.
  • the A,B, C have a value of below 30 mm, preferably 20 mm or below and preferred 10 mm or below.
  • a stir bar having a length C below 30 mm, preferably 20 mm or below and preferred 10 mm or below.
  • the adsorbent article may be described by a diameter A and a length B.
  • the parameters A and B preferably have a value of below 30 mm, preferably 20 mm or below and preferred 10 mm or below.
  • parameters A and B might have different values.
  • stir bar having a length B below 30 mm, preferably 20 mm or below and preferred 10 mm or below and having a diameter A below 5 mm.
  • the adsorptive article has no specific receiving zone for detection of a particular analyte. Moreover the adsorptive article preferably has no detection zone for determining the presence of a specific analyte.
  • Specific receiving zone means e.g. an antibody to a particular analyte.
  • Detection zone means a reaction site that gives a signal when a specific analyte is present, such as a biosensor, enzyme reaction system, or antibody.
  • the adsorbent material is included in a housing having a plurality of apertures.
  • the apertures are located in a manner that they allow a free flow of a fluid such as water into and out of the housing.
  • the size of apertures is such that the adsorbing material is prevented from leaving the apertures and permitting the fluid to be analysed to flow freely into and out of the housing.
  • the size of the holes ranges from 0.05-5 mm, preferably from 0.1-2 mm and more preferred from 1-1.5 mm.
  • the housing is made of a chemically inert material, such as ceramic (transition metal oxides), metal, porcelain or glass. Preferred are porcelain or glass. Most preferred is glass.
  • plastic it can be selected from PET (polyethylenterephtalate), PETG (polyethylenterephtalate, glycol modified), PBT (polybutylenterephtalate), PC (polycarbonate), PVC (polyvinylchloride), PP
  • PE polypropylene
  • PS polyethylene, including low density and high density PE
  • polyamide such as nylon
  • LCP liquid crystal polymer
  • TPE-E Thermoplastic
  • the plastic material preferably has no pores but has a smooth surface.
  • the shape and the size of the housing is adapted to the place where the analyses should take place.
  • Thickness A, a width B and a length C of the housing, e.g. capsule, have preferably a value 5 mm higher than those from the adsorbent article.
  • the housing may have the shape of a tube, where one or both ending could be removable.
  • the tube may have a length from 0.5 cm - 5 cm, preferably from 1-2 cm.
  • the housing may have one flat side, e.g. the housing might have the shape of tube which is cut in the middle. One or both endings of the "half-tube" might be closed with a removable lid.
  • the housing may have a length from 0.5 cm - 5 cm, preferably from
  • the tube having a diameter from 0.5 cm -1 cm and having a length from 1-2 cm for example is suitable for analysing compounds in body cavities such as the mouth, vaginal or anal cavity, or armpits.
  • Housings having a flat side are suitable for analysing portions of the skin.
  • the apertures may be located at their longer site.
  • the housing may have any other shape suitable for the present invention. Shapes include spherical, cubical, or a random shape which can be adapted, e.g., to the respective area of the body.
  • the adsorbing material included within the housing material may have the form of a powder, fibers, beads, glass beads coated or linked with the adsorbent material, capsules, micro-capsules, pellets micro-pellets, or a sheet, film or foil of the adsorbing material.
  • the adsorbent material might be plain, porous or hollow.
  • the sheet , film or foil might be folded.
  • the adsorbent material is adapted to the housing, e.g. beads of adsorbent material such as PDMS orTenax might have a diameter from more than 0.05 mm to below 10 mm.
  • beads comprising PDMS (consisting of PDMS or coated with
  • PDMS PDMS
  • having a diameter from more than 0.05 mm to below 10 mm, preferably from more than 0. 5 mm to below 5 mm and most preferred from more than 1 mm to 2 mm.
  • a magnetic stirrer may be placed additionally within said housing.
  • the magnetic stirrer might be coated with the adsorbing material. In this case no additional adsorbing material has to be present, but might be.
  • the adsorbent material is chemically inert, and does not release any compounds.
  • the adsorbent material preferably is capable to adsorb odorants or tastants. All materials as mentioned above are suitable. Preferred materials are PDMS and
  • the adsorbent material is removable from the housing.
  • the term "removable” means in this context that the adsorbent material is not physically attached to the housing.
  • the adsorbent material is free flowing within the housing.
  • the adsorbent article comprises a means for ensuring the safety of the subject, particularly when an oral application is contemplated.
  • a means can be a fixing, holding and/or retrieving means.
  • Particular examples of such a means include a string, thread, wire or hook.
  • the adsorbent material may be introduced into capsule.
  • the term apertures means that the capsule is porous to allow an unhindered penetration of air and saliva to the adsorbent article.
  • the capsule preferably is made from glass and closed with a cap. Thickness A, a width B ,and a length C of the capsule have preferably a value 5 mm higher than those from the adsorbent article.
  • the pore size may vary from 0.5-5 mm, preferred from 1-2 mm.
  • the parameters such as surface of the adsorbing material, period of contact, size of the adsorbing article may be varied according to the needs.
  • the surface of the adsorbing material may chosen in a way, that the absorption is in relation to the threshold of detection.
  • food liquid or solid
  • beverages such as fruit juice, mineral drinks, lemonade, infusions, alcoholic drinks including wine and beer, caffeine drinks such as coffee, espresso, cappuccino, black or green tea, energy drinks
  • matrixes enriched with compounds to be analysed pharmaceutical compositions, mouthwashes, toothpaste, tobacco-ware especially smoke thereof (i.e. smoke from cigarettes, pipes, cigars) or perfumes.
  • topical composition (to be administered prior to the extraction of the analytes) comprises ointments pastes, lotions, creams, gels, sun creams, perfumes, shampoos, soaps, skin care, showering gels, body rinsing materials, TTS (transdermal therapeutic systems). Topical compositions may be used cosmetically or therapeutically.
  • analyte means any compound that may be analysed.
  • the term relates to any compound to be administered orally or topically or to the nasal vaginal or anal cavity.
  • the analyte may be ionic or non-ionic, polar , non-polar or semipolar.
  • analyte includes pharmaceutical actives, cosmetic actives, adjuvants, hormones, pheromones, proteins, toxic compounds (e.g. environmental toxics), carbohydrates, fats, tastants or other compounds inducing any kind of chemo- or physio-perception, types of compounds that elicit a trigeminal sensation either in the nasal, oral, or pharyngeal area, volatiles, or odours.
  • Preferred analytes are tastants, volatiles, and odorants. Most preferred are odorants.
  • Tastants are defined as compounds interacting with taste receptors located in taste buds of the tongue. Five important basic taste perceptions exist: sour, sweet, bitter, salty and umami.
  • Chemo-reception or physio-perception e.g. means compounds that elicit sensations of heat, coolness, astringency, spicy, burning or hot sensations, pungent soapy or fizzy sensations, perceptions of creaminess or other types of mouth feeling.
  • Odorants are volatile compounds which are perceived by the odour receptor sites of the smell organ i.e. the olfactory tissue of the nasal cavity.
  • the aforementioned odorants may be largely classified into aldehydes, esters, acids, ketones, aromatic compounds, ethers, and epoxides.
  • odorant comprises naturally occurring odorants, precursors thereof, or synthetically prepared odorants or precursors thereof.
  • analyte also includes degradation products or metabolites of compounds included within the composition to be administered orally.
  • analyte includes compounds that degradate to odorants or degradation products of odorants.
  • the term also relates to odorants which are formed within the oral cavity.
  • oral administration means: putting a composition into the mouth or inhalation of a composition, where the compositions optionally is kept in the oral cavity, rinsed or masticated in the mouth or kept in the respiratory tract (for inhalation) for a determined period of time and finally swallowed, spit out or exhaled.
  • Topical administration means :
  • Contacting an adsorbent article with saliva means introducing the adsorbent article into the mouth.
  • Starting point means a defined moment after administration of a composition to the body.
  • Starting point after oral administration of a composition defines a moment where the adsorbent article is put into the mouth after administration of a composition into the mouth or after inhalation of a composition .
  • the starting point may be a moment where the composition is still in the mouth.
  • a moment after elimination of the composition from the mouth such as a defined moment after swallowing, spitting out, or exhalation of the composition.
  • the starting point can be any moment between 0 sec and 48 h after putting a composition into the mouth or after elimination of the composition of the mouth.
  • the starting point is selected from 15 sec to 2h, more preferably from 15 sec to 25 min after elimination.
  • the starting points may vary.
  • the starting point of the first determination will be 15 sec
  • the starting point of the second determination will be 30 sec
  • the starting point of the third determination will be 60 sec. Variation thereof will be a matter of routine for the skilled worker.
  • the composition is administered topically, or to the vaginal, anal or nasal cavity the starting defined the moment where the adsorbent article is applied to the defined area after administration of the composition or after removal such as washing of the composition. If not otherwise stated herein it defines the interval after administration of the composition.
  • the period of extracting the analyte from the defined area of the body ranges from 1 min to 24 h, preferably from 1min to 1 h.
  • the period of extracting is preferably from 1-10 min, more preferably from 2-5 min, more preferably from 4-5 minutes and preferred 5 min.
  • the period of extracting is preferably from 1 min to 5 h, more preferably from 10 min to 2 h, preferred from 10 min to 1 h, most preferred 30 min.
  • Extraction period from saliva means a defined period in which the adsorbent article stays in contact with 1 the saliva.
  • the adsorbent article may be kept within a defined area of the mouth, e.g. sublingually, on the tongue in the cheek, etc.
  • the use of an adsorbent article which is protected from contact with the oral tissue, i.e. by a capsule (see adsorbent article) may be advantageous.
  • the extraction time may be selected from 1-10 min, more preferably from 2-5 min, more preferably from 4-5 minutes and preferred 5 min.
  • Desorption means release of the analytes from the adsorbent article.
  • Desorption is mainly dependant form the chemical and physical properties of the analyte.
  • the adsorbent article may optionally shortly rinsed with purified water and dipped on a clean paper tissue to remove water droplets prior to desorption.
  • Desorption can be carried out by liquid desorption.
  • a preferred solvent may be acetonitril, methanol, ethanol, or ethylacetat, Ethers such as diethylether, or dichloromethan. Appropriates techniques such as the use of ultrasound are known in the art.
  • Desorption also can also be carried via thermal desorption. Desorption temperatures are primarily dependent by the volatility of the analyte and is typically between 150-
  • Thermal Desorption can .be accomplished by flow of a carrier gas such as helium. Thermal Desorption may be combined with cold trapping and reconcentration (cryofocusing).
  • Detection means detecting the presence of the analytes and optionally quantifying.
  • Samples may be analyses by HPLC or LC.
  • MS mass spectroscopy
  • UV UV may be used.
  • the sample may be derivatised. This method is especially relevant for liquid desorption. Volatile analytes preferably are analysed by GC.
  • FID/Olfactometry MS/Olfactometry For detection MS, FID, chemosensors, artificial noses, Olfactometry or combinations thereof, such as FID/Olfactometry MS/Olfactometry may be used. Preferred is detection by high-resolution gas chromatography-olfactometry (HRGC/O) Olfactory is the determination of compounds by nasal receptors.
  • HRGC/O gas chromatography-olfactometry
  • the retronasal threshold advantageously is taken into account.
  • the retronasal threshold may be correlated to the GC/Olfactometry detection, meaning that mainly concentrations are detected that are relevant for retronasal perception.
  • Sensitivity of GC/Olfactory detection may be influenced by gas flow through the GC, desorption time, sniffing port temperature, oven temperature program, material of the stationary phase.
  • adsorption to the adsorbent article may be varied in order to obtain correlation between retronasal relevance and detection.
  • the adsorbent article prior to desorption may be introduced into a sample comprising standards prior to desorption.
  • those standards are isotope labelled analytes.
  • These analytes may be present in an amount relevant for retronasal perception.
  • Figure 1 Perforated glass capsules for intraorai application of SBSE bars in BOSS- analysis.
  • Figure 2. Initial retronasal intensity during oral application of the single odorant solutions versus retronasally perceived persistence of the same odorants.
  • Figure 4 Time-resolved retronasal evaluation of the intensities of odor attributes and their overall odor intensities (middle graph) after intraorai application and expectoration of strawberry aroma samples in water and milk, respectively.
  • Figure 7 Time-resolved (15, 30, 60, 120, 240 sec) intraorai odorant detection by BOSS after expectoration of strawberry aroma samples in water and milk, respectively.
  • Figure 8 Time-resolved retronasal evaluation of the intensities of odor attributes and their overall odor intensities (middle graph) after intraorai application and expectoration of two Chardonnay wines.
  • FIG. 10a housing including an adsorptive material suitable to be introduced into the mouth, vagina, anal cavity, nose, under the armpits or for solid phase extraction.
  • A adsorbent material
  • B Housing (tube);
  • C apertures;
  • D releasable closing
  • FIG. 10b housing including an adsorptive material suitable to be introduced into the mouth, vagina, anal cavity, nose, under the armpits or for solid phase extraction.
  • A adsorbent material
  • B Housing (capsule);
  • C apertures;
  • Figure 10c housing including an adsorptive material suitable to be applied onto the skin
  • A adsorbent material
  • B Housing (tube cut in the middle);
  • C apertures;
  • D releasable closing
  • FIG. 10d housing including an adsorptive material suitable to be applied onto the skin
  • A adsorbent material
  • B Housing (watch glass);
  • C apertures
  • FIG. 10d patch including an adsorptive material suitable to be applied onto the skin
  • A adsorbent material
  • E adhesive layer
  • F backing layer
  • G optional fixing means for the adsorbent material to the backing layer
  • odorants were obtained from the suppliers shown: ethyl butanoate, ethyl 2-methylpropanoate, ethyl 3-methylbutanoate, ethyl hexanoate, butane-2,3- dione, pentan-2,3-dione, 2-furfurylthiol, hexanal, (Z)-3-hexenol, 2,5-dimethyl-4- hydroxy-3(2H)-furanone, 3-isobutyl-2-methoxypyrazine, 2-ethyl-3,5-dimethylpyrazine, 3-(methylthio)-propanal, 3-methylbutanal, 2-/3-methylbutanoic acid, (E,E)-2,4- nonadienal, (E)-2-nonenal, octanal, ⁇ -decalactone (Aldrich, Steinheim, Germany), acetic acid, butanoic acid, 2-methoxyphenol, vanillin
  • the strawberry aroma was obtained from Givaudan (D ⁇ bendorf, Switzerland). The composition of the aroma is given in Table 1. Chardonnay Wines
  • Twister®-SBSE bars (Gerstel GmbH, M ⁇ hlheim a/d Ruhr, Germany) in the sizes given in Table 2 were used. Prior to analysis, the bars were subjected to a condition procedure according to the suppliers recommendations: the stir bars were first soaked in 100 % acetonitril for at least two days, then conditioned at 300 °C for 4h.
  • each SBSE bar was first screened for odorants ("background”, see “Results and Discussion") and then directly applied for analysis. Each stir bar was used for just one single experiment, then reconditioned and screened for background again. Each experiment was performed with at least three different SBSE bars to avoid SBSE bar variation. Encapsulation of the SBSE bars
  • adapted glass capsules were designed (cf. Figure 1). For the 20 mm bars, the total length of the capsule was 25 mm, for the 10 mm bar 15 mm. The inner diameter was in both cases 5 mm. The capsules were sealed with a glass stopper. To allow unhindered penetration of air and saliva, the capsules were regularly perforated with pores (1-2 mm diameter) with a distance of about 3 mm between pores.
  • aqueous odorant model solutions 1.0 % stock solutions of the single odorants in absolute ethanol were freshly prepared and diluted with deodorized water prior to analysis to obtain 500 mL of single aqueous solutions of each odorant (concentration: 100 ⁇ g/L and 1000 ⁇ g/L water, respectively). From these, the respective concentrations of the odorants at their retronasal odor threshold values (ROTV), at 10-fold lower concentrations (0.1 ROTV) or at the concentrations given in Table 1 were prepared by further dilution with deodorized water.
  • ROTV retronasal odor threshold values
  • 0.1 ROTV 10-fold lower concentrations
  • concentrations given in Table 1 were prepared by further dilution with deodorized water.
  • the aroma stock solution was diluted with pure EtOH. From this aroma solution 100 ⁇ L were pipetted into 100 mL of water or milk (3,5 % fat, UHT) to obtain the final odorant concentrations as given in Table 1.
  • Panelists were non-pregnant volunteers (non-smokers) of the Technical University of Kunststoff, exhibiting no known illnesses at the time of examination and with normal olfactory and gustatory function. Subjective aroma perception was normal in the past and at the time of examination.
  • the panelists had a normal salivary flow and were selected for their excellent oral hygiene, thereby not suffering from oral diseases and nuisances, such as plaque, caries, tartar, gingivitis and periodontis.
  • Intra-oral analyses were performed 2 hrs after breakfast and thorough cleaning of the teeth and oral cavity with a commercial toothpaste (5 min) and with a commercial alcohol- free, low-aromatized and antimicrobial mouthwash. Prior to oral application of the sample, the oral cavities of the panelists were screened for odorants ("blank", see Discussion chapter).
  • Thermodesorptive Sample Application Thermodesorption of the samples was performed by means of a TDS-2 thermodesorption system (Gerstel GmbH) in combination with a CIS-4 PTV injector (Gerstel GmbH) for cryofocusing the analytes prior to transfer onto the analytical column.
  • the following sampling parameters were used: Splitless thermal desorption was performed by programming the TDS-2 from 40 °C to 240 °C (5 min) with a rate of 60 °C.
  • Cryofocussing was performed with liquid nitrogen at -100 °C.
  • Injection was performed with a ramp of 12 °C/s from -100 °C to 240 °C (5 min).
  • the gas chromatographic conditions are given below.
  • the one- or a two-dimensional gas chromatography system consisted of a Mega 2 gas chromatograph (Fisons Instruments, Mainz-Kastel, Germany) as the precolumn system in tandem with a Fisons GC 5160 as the main column system.
  • the following fused silica columns were used: DB-FFAP (30 m x 0.32 mm i.d., 0.25 ⁇ m FD, J & W Scientific, Folsom, USA) and/or DB-5 (SE-54; 30 m x 0.32 mm i.d., 0.25 ⁇ m FD, J & W Scientific, Folsom, USA).
  • the gas chromatographic conditions were the same as described previously (19).
  • odorants were analysed by two-dimensional gas chromatography (TD-HRGC) as described above. MS analyses were performed with an ITD-800 (Fisons Instruments,
  • DB-FFAP (30 m x 0.32 mm i.d., 0.25 ⁇ m FD, J & W Scientific, Folsom, USA) in combination with DB-5 (SE-54; 30 m x
  • odorants were identified by comparing them with the respective reference compounds on the basis of the following criteria: odor quality, odor intensity, retention indices on two capillaries of different polarity (FFAP, SE-54), as well as mass spectra obtained by MS(EI) and MS(CI).
  • HRGC/O was at least performed three times by three different panelists at different days.
  • the PDMS-coating parameters of the commercially available SBSE-bars are given in Table 2. At the beginning of the experiments, the smallest bar (A) with the lowest thickness of coating and, consequently, the lowest total amount of PDMS was selected. Preliminary investigations showed that the applied SBSE-Bars are applicable intra-orally without any toxicological harm (22).
  • odorants should be at least present at their ROTV to elicit retronasal aroma perception upon swallowing. Therefore, the following investigations were based on the assumption that for sufficient sensitivity the SBSE system should be capable of detecting odorants at their retronasal odor threshold level (ROTV). This should be preferably valid under the in-vivo extraction conditions and with the parameters used. To proof the sensitivity of the SBSE extraction system under these conditions, aqueous odorant solutions at ROTV level were prepared. Extraction parameters were then adopted from the in-vivo conditions used (see below), that means extraction was performed for only 5 min in 1 mL of sample.
  • ROTV retronasal odor threshold level
  • This volume corresponds to the amount of saliva, which was found to be present in the oral cavity at rest (prior to the normal repeated swallowing).
  • 29 odorants from different substance groups were selected for investigation.
  • the diversity of the odorants not only with respect to their odor qualities and odor thresholds, but also to their physicochemical parameters (logP values, molecular weight) can be seen from Table 5. Despite these differences it could be shown, that all compounds were detectable under the given extraction conditions. Furthermore, it was found with only one exception ( ⁇ -decalactone), that no detection occurred for all compounds at 10-fold lower concentration (0.1 ROTV).
  • Retronasal Sensory Evaluation of Single Odorant Solutions versus BOSS In addition to the proof of in-vitro detectability of the odorants at their ROTV using the extraction parameters discussed above, the in-vivo performance of the BOS-System was investigated in comparison to the retronasally perceived persistence of the respective odorants: Retronasal Sensory Evaluation
  • the odorants were screened for their detectability after application to the oral cavity (cf. Intra-oral Sampling of Odorants) using the BOS-System.
  • the total detection times of both approaches, the analytical using the BOS-system, as well as the sensory by retronasal evaluation of persistence are plotted against each other in Figure 3.
  • the correlations between the results obtained by both techniques are striking.
  • the results strongly emphasize that the short-persistence odorants are indeed not present for longer time in the mouth and that on the other hand the sensory perception is precisely correlated to the presence of odorants in the mouth.
  • the odor qualities citrus, buttery, sweaty, vanilla, grassy, caramel, peach, flowery and fruity were selected. They were either attributed by the panelists as descriptors for the aroma mixture or for the single compounds. Then, the intensities of these odor qualities as well as the overall odor intensities were rated comparatively both in the aromatized water and milk samples at given times (cf. spider web graphs in Figure 4). In parallels, the overall aroma intensities should be rated at the same times (cf. small bar diagrams in Figure 4). When first looking at the overall aroma intensities and their persistence with time, it becomes evident that the water sample elicits a considerably higher aroma impression than the milk sample from the beginning until the end of evaluation.
  • vanilla note was at first (30 sec) rated as more perceivable in the milk sample but persisted then longer (2 min) in the water sample as compared to the milk sample (1 min). The reasons for this have not been seized at present. It can be assumed that the dominant sweet, flowery and fruity impressions at the beginning of the evaluation lead to an overestimation of the vanilla-note. From a quantitative point of view, there is probably too much vanillin already present due to the aromatization so that the minor additional amounts originating from the milk (more than 100-fold lower than in the strawberry aroma, 24) cannot be expected to play any significant sensory role. Generally, the difference between the overall aroma impressions of both samples (water and milk) was rated with 2.8 on the 0.0 to 3.0 scale as very high. BOSS
  • grassy compounds hexanal and (Z)-3-hexenol as well as the fruity compounds ethyl butanoate, ethyl isopentanoate, ethyl hexanoate, (Z)-3-hexenyl acetate, as well as methyl dihydrojasmonate were detectable by BOSS only for a relatively short period of time (up to 2 min), while the sweet and flowery compounds ⁇ -ionone, methyl cinnamate, methyl anthranilate and the coconut-like ⁇ -decalactone were even detectable after 4 and 8 min, respectively.
  • the concentrations of these compounds might be sufficient for detection in the concentrated solvent extracts obtained from 100 mL of the respective wines (see Experimental), but not high enough to be of retronasal sensory relevance (see below, Quantitation of the Potent Wine Odorants).
  • Most odorants were detectable in both wines at the starting point of BOSS evaluation (15 sec after swallowing). The only exceptions were sotolone, eugenol, 2-methoxyphenol, cis- and trans-whiskeylactone and methional, which were only detectable after consumption of the Merryvale wine, while 3-methylbutyl acetate was missing here.
  • both wines simply contain different amounts of the respective odorants, resulting in higher intensities and persistences. This will be discussed in the following chapter. Also, there might be differences in the matrix composition of the wines so that the intra-oral release parameters might be changed. In this context, it also has to be mentioned that the ethanol content of both wines was not completely equal (Merryvale 14.5 % by vol., Forest Hill 13.5 % by vol.). Whether this difference has an effect e.g. on odorant-mucosa interactions and, as a consequence, on retronasal perceptibility with time, needs to be further investigated.
  • Table 7 shows the concentrations of these odorants in both wines together with the respective mass traces analysed in SI DA.
  • the technique described herein offers, for the first time, the possibility to strike the balance of food odorants in-vivo.
  • adsorption of odorants to oral mucosa under precisely defined conditions can be quantified according to the SOOM-approach. Release therefrom into salivary and air phases present in the oral mucosa can now not only be detected but also quantified by exposing the stir bar after oral application to suitable standards preferably stable isotope labelled standards. Feasibility of this approach has already been proofed (unpublished data) and the validation of this technique and some in-vivo applications will be published soon.
  • the amounts being transferred to the olfactory area can now be not only be detected but also exactly quantified even in trace concentrations as it has been shown recently (28).
  • the volatiles including key odorants are collected from the nose (or mouth) by trapping the exhaled air. This can be achieved for example by cryofocusation as it was done previously using a glass tube or glass helix where the air is led through and which is immersed into liquid nitrogen (29).
  • Other techniques such as TENAX-trapping as described previously in the EXOM-Approach are also possible (30).
  • Collection of the trapped odorants from the frozen breath can be achieved for example by solvent uptake or also by introduction of e.g. an SBSE-bar into the aqueous breath phase or any other adsorptive device capable for collecting the respective odorants.
  • an SBSE-bar into the aqueous breath phase or any other adsorptive device capable for collecting the respective odorants.
  • Vanillin vanilla-like 2567 1397 0.6-1.2 a Retention indices were calculated according to (32).
  • the odor threshold values in air were determined as described elsewhere (33).
  • MW Molecular Weights
  • ROTV Retronasal Odor Threshold Values
  • Vanillin vanilla-like 30 152 1.08 a logP values were calculated according to (34)
  • (2S 3 8aR)-3 3 4-Dihydro-3-oxoedulan,- j In ⁇ the, ⁇ xture 3 of 3 2S 3 8aS 3 (see,below), ⁇ e 3 dominated
  • Acyclics 3 (Alcohols prescriEsters operatesAcids sanctionAldehydes) (R)-(+)-2-methylbutanol,- 3 ferrnented, 3 fetty (S)-(-)-2-methylbutanol,-,ethereal utilizatfresh (S)-(+)-2-methylbutanal,- ,pungent,,ftesh facilitator:rrmty 3 (Boelens 33 et.,al.); 3 Pec ⁇ Bartschat,et.,al) (R)-(-)-2-methylbutanal,- ,pungent,,capryHc,(Boelens sanctionets,al.); 3 PecuHa ⁇ (3 S)-3 - ethylpentanal,- ensive 3 green 3 ,fresh 3 ,in,tagh,concentt ,a,srigntly,pungent,odor (3R)-3-methylpenta ⁇ al,- 3 No,rragrance 3 impression

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Abstract

L'invention porte sur un procédé visant à déterminer qualitativement ou quantitativement un ou plusieurs analytes présents dans une zone définie du corps d'un sujet, ce procédé se caractérisant par: a) l'application d'un matériau adsorbant sur la zone définie du corps du sujet ; b) l'extraction de l'analyte de cette zone et l'élimination du matériau adsorbant de ladite zone du corps ; c) la désorption de l'analyte du matériau adsorbant et d) la détection de l'analyte qualitativement ou quantitativement. La présente invention porte, en outre, sur un article adsorbant ou un système transdermique approprié pour être appliqué dans ce procédé et sur l'utilisation de l'article adsorbant ou du système transdermique pour déterminer qualitativement ou quantitativement un ou plusieurs analytes.
EP04763355A 2003-09-07 2004-07-20 Detection d'analytes dans une zone definie du corps Withdrawn EP1664728A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110567909A (zh) * 2019-09-10 2019-12-13 福建中烟工业有限责任公司 一种检测诱捕器芯片中性外激素含量的方法

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2008691A1 (fr) * 2007-06-29 2008-12-31 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Odorisants vaginaux
WO2009060317A2 (fr) * 2007-11-08 2009-05-14 Imperial Innovations Ltd Procédés de diagnostic et de suivi de l'évolution d'une maladie et d'évaluation des effets de la thérapie utilisant une matrice absorbante
EP2233206B1 (fr) * 2009-03-24 2015-07-29 Symrise AG Dispositif d'extraction de saveur pour l'isolation ou l'analyse de composants volatiles
CN102004135B (zh) * 2010-10-26 2013-03-27 中山大学 解吸池及分子印迹搅拌棒微萃取-高效液相色谱在线联用装置
CN102288473B (zh) * 2011-05-10 2013-02-13 中山大学 动态液液固印迹微萃取-液相色谱在线联用系统
EP2841939A4 (fr) 2012-04-26 2015-11-25 Niva Procédé de détoxification ou de mesure d'au moins un composé ou d'au moins un fluide dans un corps hôte
JP6470526B2 (ja) * 2014-08-26 2019-02-13 小川香料株式会社 香気成分の香気発現特性の評価方法
CN107003298B (zh) 2014-11-27 2020-04-14 皇家飞利浦有限公司 尿液和粪便蒸汽的化学分析
CN104569263B (zh) * 2014-12-29 2017-01-04 中国烟草总公司山东省公司 一种快速准确评价卷烟产品质量稳定性的方法
CN108195947A (zh) * 2017-10-18 2018-06-22 谢华 一种人体自然体香的采样分析方法
KR102444774B1 (ko) * 2017-12-27 2022-09-19 오씨아이 주식회사 카본 블랙의 표면 관능기의 정량 및 정성 분석 시스템 및 방법
CN110554113B (zh) * 2019-09-12 2022-04-01 云南中烟工业有限责任公司 一种基于sbse-hs-gc-ms烟丝中挥发性成分的检测方法
CN110554115B (zh) * 2019-09-20 2022-04-01 云南中烟工业有限责任公司 一种基于sbse-td-gc-ms的烟丝中的挥发性成分测定方法
CN112213423B (zh) * 2020-09-30 2022-03-01 青岛啤酒股份有限公司 同时检测啤酒/麦汁中多种挥发性酚类异味的方法
WO2022072827A1 (fr) * 2020-10-02 2022-04-07 Sensill, Inc. Dispositifs, procédés et systèmes pour collecter, stocker et analyser des substances chimiques
CN113960236B (zh) * 2021-10-11 2023-07-25 大连海洋大学 一种基于快速前处理技术测定鱼体中土臭素和二甲基异莰醇的方法
CN118883775B (zh) * 2024-09-29 2024-12-20 济南悟通生物科技有限公司 一种检测芬美檀香手性异构体的方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4046014A (en) * 1975-06-20 1977-09-06 Boehringer John R Sealable activated charcoal gas sampler
US6627226B2 (en) * 1988-10-05 2003-09-30 Whatman, Inc. Dry solid medium for storage and analysis of genetic material
FR2695208A1 (fr) * 1992-08-25 1994-03-04 Inocosm Laboratoires Procédé de prélèvement et de concentration de produits volatils, issus de la peroxydation des acides gras poly-insaturés, ainsi que dispositifs permettant la mise en Óoeuvre de ce procédé.
US5479815A (en) * 1994-02-24 1996-01-02 Kraft Foods, Inc. Method and apparatus for measuring volatiles released from food products
US5725481A (en) * 1996-05-17 1998-03-10 A. Fem Medical Corporation Method and apparatus for collecting vaginal fluid and exfoliated vaginal cells for diagnostic purposes
WO1999066304A1 (fr) * 1998-06-19 1999-12-23 California Institute Of Technology Utilisation d'une olfactometrie artificielle pour detecter le niveau de presence de substances a analyser
EP1448302A4 (fr) * 2001-10-05 2007-12-05 Kenneth A Alley Appareil servant a prelever, stocker, conserver et analyser un echantillon
EP1451553B1 (fr) * 2001-11-26 2017-08-23 PAWLISZYN, Janusz B. Dispositif et procede de micro-extraction et desorption de sorbant

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005024389A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110567909A (zh) * 2019-09-10 2019-12-13 福建中烟工业有限责任公司 一种检测诱捕器芯片中性外激素含量的方法

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