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  • 251.
    R, Torgrip
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    K, Aberg
    E, Alm
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    I, Schuppe-Koistinen
    J, Lindberg
    A note on normalization of biofluid 1D 1H-NMR data2008In: Metabolomics, no 4, p. 114-121Article in journal (Refereed)
  • 252. Raison-Peyron, Nadia
    et al.
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Du-Thanh, Aurélie
    Karlberg, Ann-Therese
    Widespread contact dermatitis from unexpected exposure to rosin from a toilet seat2013In: Dermatitis, ISSN 1710-3568, E-ISSN 2162-5220, Vol. 24, no 3, p. 149-150Article in journal (Refereed)
  • 253.
    Ramzy, Ahmad G.
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Hagvall, Lina
    Pei, Mansoureh N.
    Samuelsson, Kristin
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Investigation of diethylthiourea and ethyl isothiocyanate as potent skin allergens in chloroprene rubber2015In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 72, no 3, p. 139-146Article in journal (Refereed)
    Abstract [en]

    Background

    Exposure to chloroprene rubber has resulted in numerous cases of allergic contact dermatitis, attributed to organic thiourea compounds used as vulcanization accelerators. However, thiourea compounds are not considered to be strong haptens.

    Objectives

    To analyse common commercial chloroprene materials for their contents of diethylthiourea (DETU), dibutylthiourea (DBTU), diphenylthiourea (DPTU), and their degradation products, isothiocyanates; and to investigate the sensitization potencies of possible degradation products of the mentioned thiourea compounds.

    Methods

    Liquid chromatography/mass spectrometry (MS) was used for quantification of organic thiourea compounds in chloroprene products, such as medical, sports and diving gear; isothiocyanates were measured by solid-phase microextraction/gas chromatography/MS. Sensitization potencies were determined with the murine local lymph node assay (LLNA).

    Results

    DETU was identified at concentrations of 2.7-9.4 mu g/cm(2) in all samples, whereas neither DBTU nor DPTU was detected. At 37 degrees C, degradation of DETU in the materials to ethyl isothiocyanate (EITC) was detected. EITC and ethyl isocyanate showed extreme and strong sensitization potencies, respectively, in the LLNA.

    Conclusions

    DETU can act as a prehapten, being degraded to EITC when subjected to body temperature upon skin contact. EITC could thus be the culprit behind allergic contact dermatitis caused by chloroprene rubber.

  • 254.
    Redeby, Theres
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Altamore, Timothy A.
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Ambrosi, Annalisa
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Broo, Kerstein
    Borje, Anna
    Karlberg, Ann-Therese
    Specific Adducts Formed through a Radical Reaction between Peptides and Contact Allergenic Hydroperoxides2010In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 23, no 1, p. 203-210Article in journal (Refereed)
    Abstract [en]

    The first step in the development of contact allergy (allergic contact dermatitis) includes the penetration of an allergy-causing chemical (hapten) into the skin, where it binds to macromolecules such as proteins. The protein-hapten adduct is then recognized by the immune system as foreign to the body. For hydroperoxides, no relevant hapten target proteins or protein-hapten adducts have so far been identified. In this work, bovine insulin and human angiotensin I were used as model peptides to investigate the haptenation mechanism of three hydroperoxide haptens: (5R)-5-isopropenyl-2-methyl-2-cyclohexene-1-hydroperoxide (Lim-2-OOH), cumene hydroperoxide (CumOOH), and 1-(1-hydroperoxy-1-methylethyl) cyclohexene (CycHexOOH). These hydroperoxides are expected to react via a radical mechanism, for which 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride (Fe(III)TPPCl) was used as a radical initiator. The reactions were carried out in 1:1 ethanol/10 mM amonium acetate buffer pH 7.4, for 3 h at 37 T, and the reaction products were either enzymatically digested or analyzed directly by MALDI/TOF-MS, HPLC/MS/MS, and 2D gel electrophoresis. Both hydroperoxide-specific and unspecific reaction products were detected, but only it) the presence of the iron catalyst. In the absence of catalyst, the hydroperoxides remained unreacted. This suggests that the hydroperoxides call enter into the skin and remain inert until activated. Through the detection of a Lim-2-OOH adduct bound at the first histidine (of two) of angiotensin I, it was confirmed that hydroperoxides have the potential to form specific antigens in contact allergy.

  • 255.
    Riddar, Jakob B.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Isocyanates, Amines and Alkanolamines: Sampling, Chromatography and Detection2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Isocyanates, aromatic-, aliphatic- and alkanolamines are commonly used in the industry today. Millions of workers in Europe are exposed. The most frequent health symptoms are respiratory and dermal disorder. Due to the health risk most of the compounds in this thesis are regulated by authorities and have occupational exposure limits (OELs). Consequently, reliable and robust air sampling methods are urgently needed.

    In this thesis dry samplers for isocyanates, aliphatic- and alkanolamines have been developed and evaluated. The isocyanate sampler is now a commercial product (ASSET EZ4-NCP Dry Sampler, Supelco). The samplers were based on a denuder with a filter in series. The denuder and filter were impregnated with di-n-butylamine for the isocyanate sampler and with sulphuric acid for the aliphatic- and alkanolamine sampler.

    The robustness of the dry samplers was extensively evaluated. This was performed in a climate chamber containing a controlled atmosphere of the studied compounds.

    New methods based on hydrophilic interaction liquid chromatography (HILIC) coupled with tandem mass spectrometry (MSMS) were developed for determination of aromatic-, aliphatic- and alkanolamines in aqueous solutions. Isocyanates were determined by reversed-phase liquid chromatography MSMS.

    HILIC in combination with MS is a most powerful system, and highly sensitive determinations, several orders of magnitude below the OELs, of polar compounds present in the work environment can be accomplished.

    The selected samplers enable sampling during short sampling times and for whole work shifts. The samplers can be stored for months before and after sampling. The performance of the samplers was unaffected by variation in temperature, humidity, flow-rate and pre- and post-sampling of ambient air.

    Sampling for the compounds studied is now greatly simplified, and assessment of the work environment is facilitated.

  • 256.
    Riddar, Jakob B.
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlsson, Daniel
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Dalene, Marianne
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Skarping, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    A novel sampler for aliphatic amines and a new method for determination using hydrophilic interaction liquid chromatography tandem mass spectrometryManuscript (preprint) (Other academic)
    Abstract [en]

    A novel sampler for determination of airborne aliphatic amines is presented using hydrophilic interaction liquid chromatography (HILIC) with tandem mass spectrometry (MSMS). The sampler consisted of a denuder comprising a polypropylene tube (length = 7 cm, ID = 0.8 cm) with an inner wall coated with a glass fibre filter and internal glass fibre filter strip folded into a ‘V’ to increase the denuder surface coupled in series with a 13 mm glass fibre filter. Sulphuric acid was used for impregnation of all the filters.

    Electrospray ionisation and multiple-reaction monitoring (MRM) of the protonated molecular ions and corresponding deuterium-labelled internal standards resulted in selective determination with linear correlation coefficients > 0.995,  instrumental precision (n = 16) < 6 %  and detection limits of 1.9 - 150 pg (2.6 - 195 ng mL-1) for ethylamine (EA), allylamine (AA), isopropanol amine (IPA), n-butylamine (NBA), diethylamine (DEA), dimethylethylamine (DMEA), cyclohexylamine (CHA), diisopropylamine (DIPA) and triethylamine (TEA).

    The performance of the sampler was investigated by sampling a standard atmosphere of AA, IPA, NBA, DEA, DMEA, CHA and TEA (0.5-15.4 mg m-3) in an exposure chamber (0.3 m3). The air concentrations of the amines were generated by gas phase membrane permeation.

    The extraction recovery for spiked samplers (10-100 μg) was in the range 93-106 % (except for DMEA 127 %). The precision when sampling three series of ten samplers each was in the range 1.8-7.0 %. Collection efficiencies of > 99.9 % without breakthrough were observed for the studied amines when sampling over 60 min using four sets of two samplers in sequence at a flow rate of 200 mL min-1. Major breakthrough was observed for TEA and DMEA at 800 mL min-1 with collection efficiencies > 82 %. For CHA, DEA, NBA, IPA and AA, the collection efficiencies were > 97 %. The distribution of the aliphatic amines in the sampler was studied by dissection of the denuders (into eight parts) for two different flow rates (200 and 1100 mL min-1). The first parts of the denuder collected the highest amount of aliphatic amines, which then declined throughout the remaining parts. Thus, it was deemed that the denuder was too short to collect all gas phase amines and the presence of the end filter was necessary for efficient collection. No effect was observed on the collection efficiency when samplers were stored for up to 45 days prior to sampling. No degradation of the amines on the sampler was observed when exposed samplers were stored for up to 45 days. When sampling IPA, DEA and TEA over a period of 0.5 - 8 h (n = 6), linear relationships were obtained with correlation coefficients > 0.997. Using sampling flow rates of 50-800 mL min−1, linear relationships were obtained with correlation coefficients > 0.977. Pre- or post-exposure to ambient air for up to 10 h at 25 °C or 50 °C did not affect the sampler performance.

  • 257.
    Riddar, Jakob B.
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlsson, Daniel
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Dalene, Marianne
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Skarping, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    A novel sampler for alkanolamines and a new method for determination using hydrophilic interaction liquid chromatography tandem mass spectrometry2014In: Annals of Occupational Hygiene, ISSN 0003-4878, E-ISSN 1475-3162Article in journal (Refereed)
    Abstract [en]

    A novel sampler for determination of airborne alkanolamines is presented using hydrophilic interaction liquid chromatography (HILIC) with tandem mass spectrometry (MSMS). The sampler consisted of a denuder comprising a polypropylene tube (length = 7 cm, ID = 0.8 cm) with an inner wall coated with a glass fibre filter and internal glass fibre filter strip folded into a ‘V’ to increase the denuder surface coupled in series with a 13 mm glass fibre filter. Sulphuric acid was used for impregnation of all the filters.

    Electrospray ionisation and multiple-reaction monitoring (MRM) of the protonated molecular ions and corresponding deuterium-labelled internal standards resulted in selective quantifications with linear correlation coefficients > 0.992,  instrumental precision (n = 16) of < 6 %  and detection limits of 5.1 – 48 pg for ethanol amine (EA), n-propanol amine (NPA), isopropanol amine (IPA), dimethylethanol amine (DMEA), diethanol amine (DEA), diethylethanol amine (DEEA), methyldiethanol amine (MDEA), diisopropanol amine (DIPA) and triethanolamine (TEA).

    The performance of the sampler was investigated by sampling a standard atmosphere of EA, IPA, DMEA, DEEA and MDEA (0.03-6.1 mg m-3) in an exposure chamber (0.3 m3). The air concentrations of the amines were generated by liquid phase membrane permeation.

    The extraction recovery for spiked samplers (10 μg) was in the range 93-106 %. The precision when sampling three series of ten samplers each was in the range 2.1-4.8 %. No breakthrough was observed from the sampler when sampling during 60 min using four sets of two samplers in sequence at a flow rate of 0.2 L min-1. A minor breakthrough was observed for DEEA and DMEA at 0.8 L min-1 and the collection efficiencies were > 99.4 %. The distribution of the alkanolamines in the sampler was studied by dissection of the denuders (into eight parts) for two different flow rates (0.2 and 1.1 L min-1). The first parts of the denuder collected the highest amount of alkanolamines, which then declined throughout the remaining parts. It was observed that the denuder was too short to collect all the gas phase alkanolamines and the presence of the end filter was necessary for efficient collection. No effect was observed on the collection efficiency when samplers were stored for up to 45 days prior sampling. No degradation of the alkanolamines on the sampler was observed when exposed samplers were stored for up to 45 days. When sampling DMEA and DEEA, over a period of 0.5 - 8 h (n = 6), linear relationships were obtained with correlation coefficients > 0.998. Using sampling flow rates of 0.05 - 0.8 L min−1, linear relationships were obtained with correlation coefficients > 0.974. Pre- or post-exposure to ambient air for up to 10 h at 25 °C or 50 °C did not affect the sampler performance.

  • 258.
    Riddar, Jakob B.
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlsson, Daniel
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Dalene, Marianne
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Skarping, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Analysis of Aqueous Alkanolamines using Hydrophilic Interaction Liquid Chromatography and Mass Spectrometr2013In: Analytical Chemistry Letters, ISSN 2229-7928, Vol. 3, no 5-6, p. 298-313Article in journal (Refereed)
    Abstract [en]

    A method for determination of mono-, di-, triethanolamine (EA, DEA, TEA), iso-, N-propanolamine (IPA, NPA),  diisopropyl ethanol amine (DIPEA), 2-diethylethanol amine (DEEA), diisopropanol amine (DIPA), dimethylethanol amine (DMEA), N-methyldiethanol amine (MDEA) in aqueous solutions is presented. Separation was achieved by zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC). Injections of aqueous solutions were enabled by on-column focusing with partially filled loop injections. The ZIC-HILIC was coupled with a tandem mass spectrometer (MS/MS) with electrospray ionisation monitoring of positive ions. Linear calibration graphs (0.04-3.0 μg mL-1, n = 9) were obtained with correlation coefficients in the range of >0.96 using N-tripropyl amine (NTPN) as internal standard and >0.99 using NPA as internal standard. The instrumental detection limit was below 44 fmol.

    Chromatographic separation of the 10 studied alkanolamines was achieved. The most suitable composition of the focusing liquid was determined to be 1:1 AcCN/AcO, enabling injection volumes up to 3 µL whilst maintaining the chromatographic characteristics. The optimal solvent composition was found to be 100 % water with 0.01 % acid at pH < 4. Sample solution concentrations of 1.0 µg mL-1 could be injected on the column with sustained chromatography.

    To maintain stable chromatography the column needed to be regenerated after approximately 500 injections. A minimum of 5 minutes equilibration time between runs was required. The importance of equilibration was also observed after regeneration of the column to obtain chromatographic stability (peak shape and retention times), especially for the compounds eluting close to the front.

    Characterisation of the MS fragmentation pattern for the alkanolamines by hydrogen-deuterium exchange indicated a main loss of one or more water molecules. For secondary and tertiary alkanolamines the loss of an alkyl-group and/or alkanol-group was also seen.

    The possibility of using the method for determining alkanolamines in metal working fluids and in air samples was demonstrated.

  • 259.
    Riddar, Jakob Johnson
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlsson, Daniel
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Dalene, Marianne
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Skarping, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Determination of aromatic amines in aqueous extracts of polyurethane foam using hydrophilic interaction liquid chromatography and mass spectrometry2010In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 678, no 1, p. 117-123Article in journal (Refereed)
    Abstract [en]

    A method is presented for the determination of aromatic amines in aqueous extracts of polyurethane (PUR) foam. The method is based on the extraction of PUR foam using aqueous acetic acid (0.1%, w/v) followed by determination of extracted aromatic amines using hydrophilic interaction liquid chromatography (HILIC) and tandem mass spectrometry (MS/MS) with positive electrospray ionisation. The injections of volumes up to 5 mu L of aqueous solutions were made possible by on-column focusing with partially filled loop injections. The fragmentation patterns for 2,4- and 2,6-toluene diamine (TDA) and 4,4'-methylene dianiline (MDA) were clarified by performing a hydrogen-deuterium exchange study. TDA and MDA were determined using trideuterated 2,4- and 2,6-TDA and dideuterated 4,4'-MDA as internal standards. Linear calibration graphs were obtained over the range 0.025-0.5 mu g mL(-1) with correlation coefficients >0.996 and the instrumental detection limit for each compound was <50 fmol. The stability of the amines was influenced by the matrix, so their concentrations decreased over time. Agreement was observed between the results of analyses of PUR foam extracts by HILIC-MS/MS and results obtained by ethyl chloroformate derivatisation and reversed phase (RP) liquid chromatography-mass spectrometry (LC-MS/MS). TDA was observed to be unstable in extracts of foam but not in pure solutions.

  • 260. Rudback, Johanna
    et al.
    Bergstrom, Moa Andresen
    Borje, Anna
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlberg, Ann-Therese
    alpha-Terpinene, an Antioxidant in Tea Tree Oil, Autoxidizes Rapidly to Skin Allergens on Air Exposure2012In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 25, no 3, p. 713-721Article in journal (Refereed)
    Abstract [en]

    The monoterpene alpha-terpinene is used as a fragrance compound and is present in different essential oils. It is one of the components responsible for the antioxidant activity of tea tree oil. alpha-Terpinene is structurally similar to other monoterpenes, e.g., limonene, known to autoxidize on air exposure and form allergenic compounds. The aim of the present study was to investigate the possible autoxidation of alpha-terpinene at room temperature. To investigate the sensitization potency of air-exposed alpha-terpinene and the oxidation products formed, the murine local lymph node assay was used. Chemical analysis showed that alpha-terpinene degrades rapidly, forming allylic epoxides and p-cymene as the major oxidation products and also hydrogen peroxide. Thus, the oxidation pathway differs compared to that of, e.g., limonene, which forms highly allergenic hydroperoxides as the primary oxidation products on autoxidation. The sensitization potency of alpha-terpinene was increased after air-exposure. The allylic epoxides and a fraction, in which only an alpha,beta-unsaturated aldehyde could be identified, were shown to be strong sensitizers in the local lymph node assay. Thus, we consider them to be the major contributors to the increased sensitization potency of the autoxidized mixture. We also investigated the presence of alpha-terpinene and its oxidation products in four different tea tree oil samples of various ages. alpha-Terpinene and its oxidation products were identified in all of the tea tree oil samples. Thus, from a technical perspective, alpha-terpinene is a true antioxidant since it autoxidizes rapidly compared with many other compounds, preventing these from degradation. However, as it easily autoxidizes to form allergens, its suitability can be questioned when used in products for topical applications, e.g., in tea tree oil but also in cosmetics and skin care products.

  • 261. Rudbäck, Johanna
    et al.
    Hagvall, Lina
    Börje, Anna
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlberg, Ann-Therese
    Characterization of skin sensitizers from autoxidized citronellol - impact of the terpene structure on the autoxidation process2014In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 70, no 6, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Background. Citronellol is a frequently used fragrance compound in consumer products. It is present in fragrance mix II, which is used for screening of contact allergy to fragrances. Because of its chemical structure, citronellol could be susceptible to autoxidation. Objectives. To compare the behaviour of citronellol with that of the structurally similar compounds linalool and geraniol, in terms of ability to autoxidize, the products formed, and the sensitization potencies of these. Methods. Citronellol was exposed to air, and autoxidation was followed by gas chromatography-mass spectrometry (GC-MS) analysis after derivatization of thermolabile compounds. The sensitizing potencies of the oxidation mixture and its major oxidation compounds were examined with the local lymph node assay. Results. The concentration of citronellol decreased while the sensitization potency increased in air-exposed samples over time, with hydroperoxides being identified as the major oxidation products and main skin sensitizers. Conclusions. The present study shows the impact of the absence of the 2,3-double bond in the citronellol structure on the oxidation pathways for formation of oxidation products. The study also shows the usefulness of our new GC-MS method for quantification of the citronellol oxidation products, especially the hydroperoxides. The investigated citronellol hydroperoxides could be important allergens, owing to the high concentrations detected and frequent exposure to citronellol in the population.

  • 262. Rudbäck, Johanna
    et al.
    Islam, Nurul
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlberg, Ann-Therese
    A sensitive method for determination of allergenic fragrance terpene hydroperoxides using liquid chromatography coupled with tandem mass spectrometry2013In: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 36, no 8, p. 1370-1378Article in journal (Refereed)
    Abstract [en]

    Different compositions of monoterpenes are utilized for their pleasant scent in cosmetics and perfumes. However, the most commonly used fragrance terpenes easily oxidize upon contact with air, forming strongly skin-sensitizing hydroperoxides. Due to their thermolability and low UV absorbance, detection methods for hydroperoxides are scarce. For the first time, a simple and sensitive method using LC/ESI-MS/MS was developed to quantitatively determine hydroperoxides from the common fragrance compounds linalool, linalyl acetate, and limonene. The method was applied to autoxidized petitgrain oil and sweet orange oil. A separation was accomplished using a C3 column. The method LOD for the investigated hydroperoxides in the essential oils was below 0.3 g/mL, corresponding to 0.3 ppm. For prevention purposes and according to EU regulations, concentrations in cosmetics exceeding 100 ppm in rinse-off and 10 ppm in stay-on products of linalool and limonene must be labeled. However, the products may still contain allergens, such as hydroperoxides, formed by oxidative degradation of their parent terpenes. The sensitivity and selectivity of the presented LC/MS/MS method enables detection of hydroperoxides from the fragrance terpenes linalool, linalyl acetate, and limonene. However, for routine measurements, the method requires further validation.

  • 263. Rudbäck, Johanna
    et al.
    Ramzy, Ahmed
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlberg, Ann-Therese
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Determination of allergenic hydroperoxides in essential oils using gas chromatography with electron ionization mass spectrometry2014In: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 37, no 8, p. 982-989Article in journal (Refereed)
    Abstract [en]

    Fragrance monoterpenes are widely used commercially due to their pleasant scent. In previous studies, we have shown that air-exposed monoterpenes form hydroperoxides that are strong skin sensitizers. Methods for detection and quantification of the hydroperoxides in essential oils and scented products are thus desirable. Due to thermolability and low UV absorbance, this is a complicated task. We have recently developed a sensitive LC-ESI-MS method, but with limited structural information and separation efficiency for positional isomers and stereoisomers. In the present study, we investigated derivatization with a trimethyl silyl reagent and subsequent GC with electron ionization MS for the determination of monoterpene hydroperoxides. All investigated monoterpene hydroperoxides could be chromatographed as thermostable trimethyl silyl derivatives and yielded the fragment m/z 89 ([OSi(CH3)(3)](+)) at a higher extent compared to corresponding alcohols. Limonene-2-hydroperoxide and four other hydroperoxide isomers of limonene were separated and detected in sweet orange oil autoxidized for two months. The concentration of limonene-2-hydroperoxide isomers was found to be 19 g/mg in total. Also isomers of linalyl acetate hydroperoxide and linalool hydroperoxide were detected in autoxidized petitgrain oil (two months). The presented GC-MS method showed concentrations in the same order as previous LC-MS/MS analysis of the same type of oils.

  • 264. Rundlof, A.K
    et al.
    Fernandes, A.P.
    Selenius, M.
    Babic, M
    Shariatgorji, M
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Nilsonne, G
    Ilag, L.L
    Dobra, K
    Bjornstedt, M
    Quantification of alternative mRNA species and identification of thioredoxin reductase 1 isoforms in human tumor cells.2007In: Differentiation, Vol. 75, p. 123-32Article in journal (Refereed)
  • 265.
    Sadiktsis, Ioannis
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Bergvall, Christoffer
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Johansson, Christer
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM). Environment and Health Administration, Stockholm, Sweden.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Automobile Tires-A Potential Source of Highly Carcinogenic Dibenzopyrenes to the Environment2012In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 46, no 6, p. 3326-3334Article in journal (Refereed)
    Abstract [en]

    Eight tires were analyzed for 15 high molecular weight (HMW) polycyclic aromatic hydrocarbons (PAN), using pressurized fluid extraction. The variability of the PAIR concentrations determined between different tires was large; a factor of 22.6 between the lowest and the highest. The relative abundance of the analytes was quite similar regardless of tire. Almost all (92.3%) of the total extractable PAH content was attributed to five PAHs: benzo[ghi]perylene, coronene, indeno[1,2,3-cd]pyrene, benzo[e]pyrene, and benzo[a]pyrene. The difference in the measured PAIR content between summer and winter tires varied substantially across manufacturers, making estimates of total vehicle fleet emissions very uncertain. However, when comparing different types of tires from the same manufacturer they had significantly (p = 0.05) different PAH content. Previously, there have been no data available for carcinogenic dibenzopyrene isomers in automobile tires. In this study, the four dibenzopyrene isomers dibenzo[a,l]pyrene, dibenzo[a,e]pyrene, dibenzo[a,i]pyrene, and dibenzo[a,h]pyrene constituted <2% of the sum of the 15 analyzed HMW PAHs. These findings show that automobile tires may be a potential previously unknown source of carcinogenic dibenzopyrenes to the environment.

  • 266.
    Sadiktsis, Ioannis
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Koegler, Johannes H.
    Benham, Timothy
    Bergvall, Christoffer
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Particulate associated polycyclic aromatic hydrocarbon exhaust emissions from a portable power generator fueled with three different fuels – A comparison between petroleum diesel and two biodiesels2014In: Fuel, ISSN 0016-2361, E-ISSN 1873-7153, Vol. 115, p. 573-580Article in journal (Refereed)
    Abstract [en]

    The fuel impact on the emission of more than 40 particulate associated polycyclic aromatic hydrocarbons (PAHs) in the molecular weight range 178–302 Da were investigated. The fuels; neat diesel (EN 590), rape seed methyl ester (B100) and a 30% w/w blend thereof (B30) were tested on a portable power generator without any exhaust aftertreatment. Gaseous emissions of carbon monoxide (CO), hydrocarbons (HC) and nitrogen oxides (NOx) were measured along with particulate emissions and its size distribution for the different fuels. Collected diesel particles were extracted using pressurized fluid extraction and analyzed using an online hyphenated liquid chromatography–gas chromatography–mass spectrometry system.

    The neat B100 and the B30 fuel produced less CO and total PAHs while the emissions of NOx and particulate matter increased compared with petroleum diesel fuel per kW h. The reduction of PAH emissions of the alternative diesel fuels were 36% and 70% for B30 and B100 respectively. While the PAH profiles for the neat diesel fuel and B30 were similar, the profile of B100 differed in the sense that the emission contained a higher percentage of PAHs with higher molecular weights. The emission of these PAHs was however larger using the neat diesel fuel with the exception for some of these higher molecular weight PAHs of which there was an increased emission using B100. Thermogravimetric analysis revealed that the collected particles from B100 contained a substantial amount of volatile components. A mass spectrometric full scan analysis suggests that these volatile components are in fact unburned or partially-burned fuel constituents.

    It is concluded that the particles originating from biodiesel combustion might be very different from those originating from petroleum diesel combustion which places new demands on the development of measurement methodologies originally developed for particulate emissions from petroleum-based fuels.

  • 267. Said, Rana
    et al.
    Pohanka, Anton
    Abdel-Rehim, Mohamed
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Beck, Olof
    Determination of four immunosuppressive drugs in whole blood using meps and lc ms/ms allowing automated sample work up and analysis2012In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 897, p. 42-49Article in journal (Refereed)
    Abstract [en]

    In treatment with immunosuppressive drugs, monitoring of blood drug concentration is needed. The aim of this work was to explore micro extraction by packed sorbent (MEPS) as a possible on-line sample preparation method in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantification of cyclosporine, everolimus, sirolimus and tacrolimus in whole blood. An automated on-line MEPS system connected with a LC-MS/MS instrument was set up. A C-8 sorbent was used for the MEPS extraction. Subsequent analysis was performed with a gradient LC system. The adduct ions [M + NH4](+) of the analytes were monitored in SRM mode for quantification. Ascomycin and cyclosporine D were used as internal standards. The chromatographic run time 2.5 min and the quantification ranges were 3-1500 ng/mL (r(2) >= 0.999, n = 6) for cyclosporine and 0.5-50 ng/mL for everolimus, sirolimus and tacrolimus (r(2) >= 0.998. 0.994 and 0.993, respectively, n = 6). Precision and accuracy were documented at three levels. Accuracy results were between 102% and 109% with precision between 2% and 13% and carry over < 0.02%. Matrix effects were characterized and found to be below 20%. The quantifications obtained were in agreement with a reference LC-MS/MS method based on protein precipitation, and results obtained from external proficiency test samples compared with the mean of all other LC-mass spectrometry methods showed good agreement. This method provides an accurate, precise and automated procedure that can be applied for therapeutic drug monitoring of immunosuppressive drugs in clinical laboratories equipped with LC-MS/MS.

  • 268.
    Saleh, Aljona
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    A bioanalytical method for quantification of thioredoxins in Bacillus anthracis by digestion with immobilized pepsin and LC-MS/MS and on-line LC/LC-MS/MSManuscript (preprint) (Other academic)
  • 269.
    Saleh, Aljona
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Analysis of drugs and proteins in biological matrices, using different types of sample preparations and mass spectrometry2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes bioanalysis of small and large molecules in biological matrices and includes screening of illegal drugs in urine with high resolution mass spectrometer, bioanalysis of MTH1 inhibitors in mice plasma and quantification of proteins in plasma and cell lysates.

    Screening of illegal drugs was based on high resolving power mass spectrometer (QTOF) and the results were compared to immunoassays. For the study, the nine most commonly abused drugs were selected for screening of a large number of authentic urine samples. Evaluation of the screening results showed that the QTOF generated a low rate of false positive and false negative results and can be used as an alternative or a complementary to immunoassays.

    In another study, a bioanalytical method for the two new anticancer targets TH588 and TH287 was developed and validated. The compounds inhibit the MTH1 protein that is required for cancer cell survival. To study the pharmacokinetic properties of the substances, a bioanalytical method was developed using a fast sample preparation followed by LC-MS/MS analysis. Validation showed that the method was linear, accurate and precise in the studied concentration range. Stability tests showed that the substances were stable in mice plasma and under different storage conditions. The study also addresses other important factors such as solubility, chromatography and fragmentation mechanisms.

    Two other studies focused on quantification of specific proteins in biological specimens; plasma and bacterial lysates. The matrices are rich in endogenous proteins making quantitative analysis of target proteins challenging. Therefore a new strategy is proposed that combines known procedures in a way it has not been used before. The methods are based on quantification with isotopically labelled peptides added after proteolytic digestion of the sample with immobilized thermolysin or pepsin. The sample digest was analysed on LC-MS/MS and LC/LC-MS/MS systems.

  • 270.
    Saleh, Aljona
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Development and validation of method for TH588 and TH287, potent MTH1 inhibitors and new anti-cancer agents, for pharmacokinetic studies in mice plasmaManuscript (preprint) (Other academic)
  • 271.
    Saleh, Aljona
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Bruno, Oscar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Granelli, Ingrid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Edlund, Per-Olof
    Digestion of Enolase and Carbonic Anhydrase as Model Proteins for Therapeutic Proteins in Blood Plasma with Immobilized Thermolysin and Quantification of Some of the Peptides by LC/LC-MS/MS2014In: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 77, no 1-2, p. 59-74Article in journal (Refereed)
    Abstract [en]

    There is a need for fast method development in the early drug discovery phase of therapeutic proteins. Thermolysin has not been used for quantification of proteins in blood plasma earlier. It is a thermostable protease which permits the use of high temperatures for fast hydrolysis of proteins. Model proteins were digested with immobilized thermolysin on agarose gel. Protein-specific peptides were selected for quantitation and quantified based on stable isotope dilution. Protein digests of blood plasma were cleaned and separated using an automated LC/LC-MS/MS system. Essential digestion parameters that influence thermolysin hydrolytic activity were optimized for high peptide yield. The validated methods were selective, linear, precise and accurate with a limit of detection of 2 nM for both proteins. The proposed strategy for method development could be valuable for quantification of proteins in blood plasma samples. The study underscores and discusses important features of the enzymatic digestion and chromatographic separation.

  • 272.
    Saleh, Aljona
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Edlund, Per-Olof
    Gustafsson, Tomas N.
    Sahlin, Margareta
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sjöberg, Britt-Marie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Granelli, Ingrid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    A Bioanalytical Method for Quantification of Thioredoxins in Bacillus anthracis by Digestion with Immobilized Pepsin and LC-MS/MS and On-line LC/LC-MS/MS2016In: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 79, no 7-8, p. 383-393Article in journal (Refereed)
    Abstract [en]

    We describe a method for the quantification of proteins in a biological matrix through digestion with pepsin. Pepsin is a gastric protease that efficiently cleaves proteins in an acidic environment. In this study, it has been used to generate peptides used for the quantification of physiologically relevant thioredoxin proteins in a lysate of Bacillus anthracis-the causative agent of anthrax. Carefully selected signature peptides for proteins that were digested with pepsin were immobilized on agarose gel. Filtered samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and by two-dimensional liquid chromatography tandem mass spectrometry (LC/LC-MS/MS) when additional selectivity was needed. Some important incubation parameters were adjusted to get the highest possible peptide yield. Escherichia coli was used as a surrogate matrix for the method development. The method was validated at a low nM range for selectivity, accuracy and precision. Validation showed that signature peptides were selective for the proteins, and that the method accuracy varied between 89 and 115 % with a precision of less than 12 %. The results from using pepsin in analyzing samples from Bacillus anthracis were similar to those previously obtained using western blot, and they validate pepsin as a suitable protease to generate signature peptides in a complex biological matrix as an alternative to trypsin.

  • 273.
    Saleh, Aljona
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Gokturk, Camilla
    Warpman-Berglund, Ulrika
    Helleday, Thomas
    Granelli, Ingrid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Development and validation of method for TH588 and TH287, potent MTH1 inhibitors and new anti-cancer agents, for pharmacokinetic studies in mice plasma2015In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 104, p. 1-11Article in journal (Refereed)
    Abstract [en]

    MTH1 is a protein that is required for cancer cell survival and is overexpressed in cancer cells. TH588 and TH287 are two new compounds that inhibit the MTH1 protein. The inhibitors were tested in pharmacokinetic studies on mice. A bioanalytical method was developed and validated for determination in mice plasma. The method was based on protein precipitation followed by LC-MS/MS analysis. The separation was performed on an Ascentis Express RP-Amide C-18 column. The mass spectrometer was operated in positive electrospray ionization mode and the analytes were determined with multiple reaction monitoring (MRM). Abundant monoisotopic fragments were used for quantification. Two additional fragments were used for conformational analysis. The recovery of the compounds in plasma varied between 61 and 91% and the matrix effects were low and ranged between -3% and +2%. The method showed to be selective, linear, accurate and precise, and applicable for preclinical pharmacokinetic studies of TH588 and TH287 in mouse plasma. Half-life (T-1/2) was <= 3.5 h and maximum concentration (C-max) ranged between 0.82 and 338 mu M for the different administration routes and compounds.

  • 274.
    Saleh, Aljona
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Stephanson, Niclas Nicolai
    Granelli, Ingrid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Villen, Tomas
    Beck, Olof
    Evaluation of a direct high-capacity target screening approach for urine drug testing using liquid chromatography-time-of-flight mass spectrometry2012In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, no 909, p. 6-13Article in journal (Refereed)
    Abstract [en]

    In this study a rapid liquid chromatography-time-of-flight mass spectrometry method was developed, validated and applied in order to evaluate the potential of this technique for routine urine drug testing. Approximately 800 authentic patient samples were analyzed for amphetamines (amphetamine and methamphetamine), opiates (morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine and codeine-6-glucuronide) and buprenorphines (buprenorphine and buprenorphine-glucuronide) using immunochemical screening assays and mass spectrometry confirmation methods for comparison. The chromatographic application utilized a rapid gradient with high flow and a reversed phase column with 1.8 mu m particles. Total analysis time was 4 min. The mass spectrometer operated with an electrospray interface in positive mode with a resolution power of >10,000 at m/z 956. The applied reporting limits were 100 ng/mL for amphetamines and opiates, and 5 ng/mL for buprenorphines, with lower limits of quantification were 2.8-41 ng/mL. Calibration curves showed a linear response with coefficients of correlation of 0.97-0.99. The intra- and interday imprecision in quantification at the reporting limits were <10% for all analytes but for buprenorphines <20%. Method validation data met performance criteria for a qualitative and quantitative method. The liquid chromatography-time-of-flight mass spectrometry method was found to be more selective than the immunochemical method by producing lower rates of false positives (0% for amphetamines and opiates; 3.2% for buprenorphines) and negatives (1.8% for amphetamines; 0.6% for opiates; 0% for buprenorphines). The overall agreement between the two screening methods was between 94.2 and 97.4%. Comparison of data with the confirmation (LC-MS) results for all individual 9 analytes showed that most deviating results were produced in samples with low levels of analytes. False negatives were mainly related to failure of detected peak to meet mass accuracy criteria (+/- 20 mDa). False positives was related to presence of interfering peaks meeting mass accuracy and retention time criteria and occurred mainly at low levels. It is concluded that liquid chromatography-time-of-flight mass spectrometry has potential both as a complement and as replacement of immunochemical screening assays.

  • 275. Sehlstedt, Maria
    et al.
    Dove, Rosamund
    Boman, Christoffer
    Pagels, Joakim
    Swietlicki, Erik
    Londahl, Jakob
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Bosson, Jenny
    Barath, Stefan
    Behndig, Annelie F.
    Pourazar, Jamshid
    Sandström, Thomas
    Mudway, Ian S.
    Blomberg, Anders
    Antioxidant airway responses following experimental exposure to wood smoke in man2010In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 7, p. 21-Article in journal (Refereed)
    Abstract [en]

    Background: Biomass combustion contributes to the production of ambient particulate matter (PM) in rural environments as well as urban settings, but relatively little is known about the health effects of these emissions. The aim of this study was therefore to characterize airway responses in humans exposed to wood smoke PM under controlled conditions. Nineteen healthy volunteers were exposed to both wood smoke, at a particulate matter (PM2.5) concentration of 224 +/- 22 mu g/m(3), and filtered air for three hours with intermittent exercise. The wood smoke was generated employing an experimental set-up with an adjustable wood pellet boiler system under incomplete combustion. Symptoms, lung function, and exhaled NO were measured over exposures, with bronchoscopy performed 24 h post-exposure for characterisation of airway inflammatory and antioxidant responses in airway lavages. Results: Glutathione (GSH) concentrations were enhanced in bronchoalveolar lavage (BAL) after wood smoke exposure vs. air (p = 0.025), together with an increase in upper airway symptoms. Neither lung function, exhaled NO nor systemic nor airway inflammatory parameters in BAL and bronchial mucosal biopsies were significantly affected. Conclusions: Exposure of healthy subjects to wood smoke, derived from an experimental wood pellet boiler operating under incomplete combustion conditions with PM emissions dominated by organic matter, caused an increase in mucosal symptoms and GSH in the alveolar respiratory tract lining fluids but no acute airway inflammatory responses. We contend that this response reflects a mobilisation of GSH to the air-lung interface, consistent with a protective adaptation to the investigated wood smoke exposure.

  • 276.
    Shariatgorji, Mohammadreza
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Novel clean-up, concentration and laser desorption/ionization strategies for mass spectrometry2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Despite valuable advantages of mass spectrometry (MS) techniques they still have drawbacks that need to be overcome, notably their sensitivity to various kinds of interfering substances and associated difficulties involved in detecting signals from analytes present in trace quantities. Thus, high quality analytical data could be acquired by improving sample pre-treatment techniques and/or ionization methods to increase ionization yields and/or avoid the generation of unwanted ions.

    In the studies this thesis is based upon, a microfluidic electrocapture system capable of trapping charged proteins/polypeptides while non-charged species such as non-ionic detergents are swept out, was used to decrease the concentration of detergent in samples containing soluble and membrane associated proteins/polypeptide. Subsequent mass spectrometric analysis yielded well-resolved mass spectra of the target analytes.

    In addition, it was found that solid phase extraction (SPE) sorbents such as graphitized carbon black (GCB), can efficiently assist the laser desorption ionization of small molecules without generating any interfering ions which inspired the fabrication of μ-traps and discs. Other matrix-free approaches demonstrated the utility of silicon nitride and oxidized GCB nanoparticles as versatile media for surface-assisted laser desorption ionization (SALDI) of small molecules.

    In this thesis it is discussed that small molecule analytes such as Polyphenols present in red wine and quaternary protoberberine alkaloids with highly conjugated systems and acidic/permanently charged functional groups can be readily analyzed without any matrix or assisting-surface.

    In summary, the microfluidic electrocapture, new laser desorption ionization methods and surfaces, as well as integrated SALDI and SPE platforms, introduced in this work extend the MS strategies allowing coverage of a wider range of samples.

  • 277.
    Shariatgorji, Mohammadreza
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Amini, Nahid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Silicon nitride nanoparticles for surface-assisted laser desorption/ionization of small molecules2009In: Journal of nanoparticle research, ISSN 1388-0764, E-ISSN 1572-896X, Vol. 11, no 6, p. 1509-1512Article in journal (Refereed)
    Abstract [en]

    Conventional matrix-assisted laser desorption/ionization mass spectrometry is limited to analyses of higher molecular weight compounds due to high background noise generated by the matrix in the lower mass region. Surface-assisted laser desorption/ionization (SALDI) mass spectrometry is an alternative solution to this problem. Nanoparticles, structured silicon surfaces and carbon allotropes are commonly used as SALDI surfaces. Here, for the first time, we demonstrate the application of silicon nitride nanoparticles as a suitable medium for laser desorption/ionization of small drug molecules.

  • 278.
    Shariatgorji, Mohammadreza
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Amini, Nahid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Thorsen, Gunnar
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Crescenzi, Carlo
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    µ-trap for the SALDI-MS screening of organic compounds prior to LC/MS analysis2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 14, p. 5515-5523Article in journal (Refereed)
    Abstract [en]

    A procedure for rapidly screening and quantitatively analyzing organic molecules is presented, in which a miniaturized solid-phase extraction (SPE) cartridge containing 0.6 mg of graphitized carbon black (the GCB-mu-trap) is used for sample pretreatment. Then surface-assisted laser desorption ionization dine-of-flight mass spectrometry (SALDI-TOF-MS) screening is followed by liquid chromatography/mass spectrometry (LC/MS) for robust quantitative analysis of samples containing analytes of interest. Liquid samples with volumes up to 100 mL were extracted using the GCB-mu-trap, and SALDI screening was performed by transferring a few particles of the GCB 4 sorbent from the mu-trap onto a stainless steel plate. Analytes were then simply ionized and desorbed by irradiating the GCB 4 particles without any further pretreatment. GCB 4 was found to be an excellent surface for the SALDI analysis of small molecules, providing spectra with very clean backgrounds. The small size of the cartridge (micropipet filter tip) results in enrichment of the analytes on a small surface area, affording low SALDI-TOF-MS detection limits. Furthermore, the removal of just a few particles from the p-trap does not significantly affect the subsequent quantitative determination. This approach offers considerable reductions in analytical costs by eliminating unnecessary SPE-LC/MS analyses.

  • 279.
    Shariatgorji, Mohammadreza
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Astorga-Wells, J
    Jornvall, H
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Microfluidic electrocapture-assisted mass spectrometry of membrane-associated polypeptides2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, p. 7116-7120Article in journal (Refereed)
  • 280.
    Shariatgorji, Mohammadreza
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Astorga-Wells, Juan
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Trends in the bioanalytical applications of microfluidic electrocapture2011In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 399, p. 191-195Article in journal (Refereed)
  • 281.
    Shariatgorji, Mohammadreza
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Astorga-Wells, Juan
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Trends in the bioanalytical applications of microfluidic electrocapture2011In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 399, no 1, p. 191-195Article in journal (Refereed)
    Abstract [en]

    Downscaled analytical tools for sample preparation have offered benefits such as higher throughput, easier automation and lower sample/reagent consumption. Microfluidic electrocapture, which is a newly developed sample preparation/manipulation system, uses an electric field to trap and separate charged species without using any solid sorbent. The feasibility of using microfluidic electrocapture is reported for separation, clean-up, concentration, microreactions and complexation studies of proteins, peptides and other biologically important biomolecules. The instrumentation and applications of microfluidic electrocapture are reviewed and an overview is provided of future perspectives offered by the current and envisaged platforms.

  • 282.
    Shariatgorji, Mohammadreza
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Spacil, Zdenek
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Maddalo, Gianluca
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Cardenas, Lourdes B.
    Plant Biology Division, Institute of Biological Sciences, University of the Philippines Los Banos, College, Laguna 4031, The Philippines.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Matrix-free thin-layer chromatography/laser desorption ionization mass spectrometry for facile separation andidentification of medicinal alkaloids2009In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 23, no 23, p. 3655-3660Article in journal (Refereed)
    Abstract [en]

    Quaternary protoberberine alkaloids belong to a pharmaceutically important class of isoquinoline alkaloids associated with bactericidal, fungicidal, insecticidal and antiviral activities. As traditional medicine gains wider acceptance, quick and robust analytical methods for the screening and analysis of plants containing these compounds attract considerable interest. Thin-layer chromatography (TLC) combined with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful technique but suffers from dilution of the TLC bands resulting in decreased sensitivity and masking of signals in the low-mass region both due to addition of matrix. This study integrates for the first time conventional silica gel TLC and laser desorption ionization mass spectrometry (LDI-MS) thus eliminating the need for any external matrix. Successful separation of berberine (Rf = 0.56) and palmatine (Rf = 0.46) from Berberis barandana including their identification by MS are demonstrated. Furthermore, a robust electrospray ionization (ESI)-MS method utilizing residual sample from TLC for quantification of berberine applying selected reaction monitoring and standard addition method is presented. The amount of berberine in the plant root prepared for the study was determined to be 0.70% (w/w). Copyright © 2009 John Wiley & Sons, Ltd.

  • 283. Sharon, M
    et al.
    Ilag, L
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Robinson, C.V
    Evidence for Micellar Structure in the Gas Phase2007In: J Am Chem Soc, Vol. 129, p. 8740-6Article in journal (Refereed)
  • 284. Sholts, Sabrina B.
    et al.
    Smith, Kevin
    Wallin, Cecilia
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Ahmed, Trifa M.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Wärmlander, Sebastian K. T. S.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. UCLA, USA.
    Ancient water bottle use and polycyclic aromatic hydrocarbon (PAH) exposure among California Indians: a prehistoric health risk assessment2017In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 16, article id 61Article in journal (Refereed)
    Abstract [en]

    Background: Polycyclic aromatic hydrocarbons (PAHs) are the main toxic compounds in natural bitumen, a fossil material used by modern and ancient societies around the world. The adverse health effects of PAHs on modern humans are well established, but their health impacts on past populations are unclear. It has previously been suggested that a prehistoric health decline among the native people living on the California Channel Islands may have been related to PAH exposure. Here, we assess the potential health risks of PAH exposure from the use and manufacture of bitumen-coated water bottles by ancient California Indian societies. Methods: We replicated prehistoric bitumen-coated water bottles with traditional materials and techniques of California Indians, based on ethnographic and archaeological evidence. In order to estimate PAH exposure related to water bottle manufacture and use, we conducted controlled experiments to measure PAH contamination 1) in air during the manufacturing process and 2) in water and olive oil stored in a completed bottle for varying periods of time. Samples were analyzed with gas chromatography/mass spectrometry (GC/MS) for concentrations of the 16 PAHs identified by the US Environmental Protection Agency (EPA) as priority pollutants. Results: Eight PAHs were detected in concentrations of 1-10 mu g/m(3) in air during bottle production and 50-900 ng/L in water after 2 months of storage, ranging from two-ring (naphthalene and methylnaphthalene) to four-ring (fluoranthene) molecules. All 16 PAHs analyzed were detected in olive oil after 2 days (2 to 35 mu g/kg), 2 weeks (3 to 66 mu g/kg), and 2 months (5 to 140 mu g/kg) of storage. Conclusions: For ancient California Indians, water stored in bitumen-coated water bottles was not a significant source of PAH exposure, but production of such bottles could have resulted in harmful airborne PAH exposure.

  • 285.
    Skarping, G
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Dalene, M
    Workplace air — Guidelines for selecting analytical methods for sampling and analysing isocyanates in air: TECHNICAL REPORT ISO/TR 17737, First edition 2007-04-012007Report (Other academic)
  • 286.
    Skoglund, Christina
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry. Lantmännen Agroetanol.
    Bassyouni, Fatma
    Stockholm University, Faculty of Science, Department of Analytical Chemistry. Centre of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo, Egypt.
    Abdel-Rehim, Mohamed
    Stockholm University, Faculty of Science, Department of Analytical Chemistry. Centre of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo, Egypt.
    Monolithic packed 96-tips set for high-throughput sample preparation: determination of cyclophosphamide and busulfan in whole blood samples by monolithic packed 96-tips and LC-MS2013In: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 27, no 6, p. 714-719Article in journal (Refereed)
    Abstract [en]

    A monolithic methacrylate packed 96-tips device was used for the extraction of the busulfan and cyclophosphamide in whole blood samples. Using a packed 96-tips set, a 96-well plate could be handled in about 2min. The key aspect of the monolithic phase is that monolithic material can offer both good extraction capacity and low-back-pressure properties. The validation of the methodology showed that the accuracy values of quality-control samples were between 99 and 113% for busulfan, and between 103 and 110% for cyclophosphamide. The inter-day precision ranged from 7.0 to 12% for busulfan and from 13 to 16% for cyclophosphamide. The standard calibration curves were obtained within the concentration range 52000nm for busulfan and from 10 to 5000nm for cyclophosphamide in blood samples. The coefficients of determination were 0.99.

  • 287.
    Spacil, Z
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Eriksson, J
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    LC-MS/MS identification of -N-methylamino-L-alanine in Cyanobacteria Chromatography and Tandem Mass Spectrometry2009Conference paper (Other academic)
  • 288.
    Spacil, Zdenek
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Eriksson, J
    Jonasson, S
    Bergman, B
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Identification of -N-methylamino-L-alanine (BMAA) in Cyanobacteria2009In: Abstracts / 12th EuCheMS International conference on chemistry and the environment: 14-17 June 2009, Stockholm university, Stockholm, Sweden, 2009Conference paper (Other academic)
  • 289.
    Spacil, Zdenek
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Eriksson, Johan
    Stockholm University, Faculty of Science, Department of Botany.
    Jonasson, Sara
    Stockholm University, Faculty of Science, Department of Botany.
    Rasmussen, Ulla
    Stockholm University, Faculty of Science, Department of Botany.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Bergman, Birgitta
    Stockholm University, Faculty of Science, Department of Botany.
    Analytical protocol for identification of BMAA and DAB in biologicalsamples2010In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 135, p. 127-132Article in journal (Refereed)
    Abstract [en]

     

    b

    -N-methylamino-L-alanine (BMAA) is a non-protein amino acid, thought to be inflicting neurodegenerative diseases related to ALS/PDC in human beings. Due to conflicting data concerning the presence of BMAA in various biological matrixes, we present a robust and sensitive method for high confidence identification of BMAA after derivatization by 6-aminoquinolyl-N

    -hydroxysuccinimidyl carbamate (AQC). The efficient sample pretreatment in combination with LC-MS/MS SRM enables chromatographic separation of BMAA from the isomer 2,3-diaminobutyric acid (DAB). The method is applicable for selective BMAA/DAB detection in various biological samples ranging from a prokaryotic cyanobacterium to eukaryotic fish.

  • 290.
    Spacil, Zdenek
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Novakova, Lucie
    Department of Analytical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
    Solich, Petr
    Department of Analytical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
    Analysis of phenolic compounds by high performance liquidchromatography and ultra performance liquid chromatography2008In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 76, no 1, p. 189-199Article in journal (Refereed)
    Abstract [en]

    Two novel chromatographic methods both based on utilization of sub-2-micron particle columns were developed for the analysis of phenolic compounds in this work. An HPLC system was equipped with C18 silica-based analytical column (50 mm × 4.6 mm, 1.8 μm) and a UPLC system with ethylene-bridged hybrid C18 analytical column (100 mm × 2.1 mm, 1.7 μm).

    In total 34 phenolic substances were divided into groups of phenolic acids, flavonoids, catechins and coumarins and were analysed in sequence using different gradient methods. System suitability test data, including repeatability of retention time and peak area, mean values of asymmetry factor, resolution, peak capacity and the height equivalent of a theoretical plate were determined for each gradient method by 10 replicate injections. The developed methods were applied in the analysis of real samples (grape wines, teas).

  • 291.
    Spacil, Zdenek
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Shariatgorji, Mohammadreza
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Amini, Nahid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Solich, Petr
    Department of Analytical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Matrix-less laser desorption/ionisation mass spectrometry of polyphenols in red wine2009In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 23, no 12, p. 1834-1840Article in journal (Refereed)
    Abstract [en]

    Matrix-assisted laser desorption/ionisation (MALDI) of small molecules is challenging and in most cases impossible due to interferences from matrix ions precluding analysis of molecules <300-500 Da. A common matrix such as ferulic acid belongs to an important class of compounds associated with antioxidant activity. If the shared phenolic structure is related to the propensity as an active MALDI matrix then it follows that direct laser desorption/ionisation should be possible for polyphenols. Indeed matrix-less laser desorption/ionisation mass spectrometry is achieved whereby the analyte functions as a matrix and was used to monitor low molecular weight compounds in wine samples. Sensitivity ranging from 0.12-87 pmol/spot was achieved for eight phenolic acids (4-coumaric, 4-hydroxybenzoic, caffeic, ferulic, gallic, protocatechuic, syringic, vanillic) and 0.02 pmol/spot for trans-resveratrol. Additionally, 4-coumaric, 4-hydroxybenzoic, caffeic, ferulic, gallic, syringic, vanillic acids and trans-resveratrol were identified in wine samples using accurate mass measurements consistent with reported profiles based on liquid chromatography (LC)/MS. Minimal sample pre-treatment make the technique potentially appropriate for fingerprinting, screening and quality control of wine samples. Copyright © 2009 John Wiley & Sons, Ltd.

  • 292.
    Spáčil, Zdeněk
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Mass Spectrometry of Biologically Active Small Molecules: Focusing on polyphenols, alkaloids and amino acids2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The foci of this dissertation are on advanced liquid chromatography (LC) separation and mass spectrometry (MS) techniques for the analysis of small bioactive molecules. In addition to discussing general aspects of such techniques the results from analyses of polyphenols (PPs), alkaloids and amino acids published in five appended studies are presented and discussed. High efficiency and well understood principles make LC the method of choice for separating analytes in many kinds of scientific investigations. Moreover, when LC is coupled to an MS instrument, analytes are separated in two stages: firstly they are separated and pre-concentrated in narrow bands using LC and then separated according to their mass-to-charge (m/z) ratios in the MS instrument. Some MS instruments can provide highly accurate molecular weight measurements and mass resolution allowing identification of unknown compounds based purely on MS data, thus making prior separation unnecessary. However, prior separation is essential for analyzing substances in most complex matrices – especially useful is the ultra-high performance LC (UHPLC). The advantages of using UHPLC rather than HPLC for the analysis of PPs in tea and wine were evaluated in one of the studies this thesis is based upon. The phenolic composition of red wine was also examined, using a novel LDI technique, following solid phase extraction (SPE). A class of small aromatic molecules (medicinally important alkaloids) also proved to be amenable to straightforward analysis, by thin layer chromatography (TLC) work-up followed by LDI-MS. Finally, a LC-MS method for monitoring neurotoxins (β-N-methyl-amino-L-alanine and 2,3-diaminobutyric acid) in complex biological matrices was developed and applied. Overall, the studies show that careful attention to the physicochemical properties of analytes can provide insights that can greatly facilitate the development of alternative methods to analyze them, e.g. by LDI.

  • 293. Sroka-Markovic, Janina
    et al.
    Johansson, Linda
    Andersson, Magnus B. O.
    Granelli, Ingrid
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Development of an HPLC Method for Determination of Related Impurities in Prilocaine Substance2012In: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 75, no 7-8, p. 329-336Article in journal (Refereed)
    Abstract [en]

    Development of a reversed phase high performance liquid chromatographic method for determination of six related impurities in prilocaine substance is reported. The test of related impurities in European Pharmacopoeia (Ph. Eur.) cannot meet the demands with the chromatographic parameters given, therefore different types of chromatographic systems and eight columns have been evaluated in the present study. A new method with a Hypercarb column was developed and validated. This method fulfils the demands in the Ph. Eur., and the validation shows that the method is selective, reproducible, linear, accurate and robust with sufficient limits of detection (0.001-0.004% of 2.5 mg prilocaine mL(-1)) and quantification (0.002-0.009% of 2.5 mg prilocaine mL(-1)).

  • 294. Stec, A. A.
    et al.
    Readman, J.
    Blomqvist, P.
    Gylestam, Daniel
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Karlsson, Daniel
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Wojtalewicz, D.
    Dlugogorski, B. Z.
    Analysis of toxic effluents released from PVC carpet under different fire conditions2013In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 90, no 1, p. 65-71Article in journal (Refereed)
    Abstract [en]

    A large number of investigations have been reported on minimising the PAH and PCDD/F yields during controlled combustion, such as incineration. This study is an attempt to quantify acute and chronic toxicants including PAH and PCDD/F in conditions relating to unwanted fires. This paper investigates distribution patterns of fire effluents between gas and aerosol phase, and the different particle size-ranges produced under different fire conditions. PVC carpet was selected as the fuel as a precursor for both PAH and PCDD/F. In order to generate fire effluents under controlled fire conditions, the steady-state tube furnace, was chosen as the physical fire model. Fire scenarios included oxidative pyrolysis, well-ventilated and under-ventilated fires. Fire effluent measurements included: carbon monoxide, carbon dioxide, hydrogen chloride, polycyclic aromatic hydrocarbons, chlorinated dibenzo-dioxins and furans and soot. The distribution patterns between gas and particle phase, and the size-ranges of the particles produced in these fires together with their chemical composition is also reported. Significant quantities of respirable submicron particles were detected, together with a range of PAHs. Lower levels of halogenated dioxins were detected in the fire residue compared with those found in other studies. Nevertheless, the findings do have implications for the health and safety of fire and rescue personnel, fire investigators, and other individuals exposed to the residue from unwanted fires.

  • 295.
    Stenberg, Filippa
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Chovanec, Peter
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Maslen, Sarah L.
    Robinson, Carol V.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Daley, Daniel O,
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Protein complexes of the Escherichia coli cell envelope2005In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 280, no 41, p. 34409-34419Article in journal (Refereed)
    Abstract [en]

    Protein complexes are an intrinsic aspect of life in the membrane. Knowing which proteins are assembled in these complexes is therefore essential to understanding protein function(s). Unfortunately, recent high throughput protein interaction studies have failed to deliver any significant information on proteins embedded in the membrane, and many membrane protein complexes remain ill defined. In this study, we have optimized the blue native-PAGE technique for the study of membrane protein complexes in the inner and outer membranes of Escherichia coli. In combination with second dimension SDS-PAGE and mass spectrometry, we have been able to identify 43 distinct protein complexes. In addition to a number of well characterized complexes, we have identified known and orphan proteins in novel oligomeric states. For two orphan proteins, YhcB and YjdB, our findings enable a tentative functional assignment. We propose that YhcB is a hitherto unidentified additional subunit of the cytochrome bd oxidase and that YjdB, which co-localizes with the ZipA protein, is involved in cell division. Our reference two-dimensional blue native-SDS-polyacrylamide gels will facilitate future studies of the assembly and composition of E. coli membrane protein complexes during different growth conditions and in different mutant backgrounds.

  • 296.
    Stensland, Birgitta
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    On the conformation of dopamine D-2 antagonists: crystal structure studies of some substituted benzamide compounds1995Doctoral thesis, comprehensive summary (Other academic)
  • 297.
    Tamburro, Davide
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Candidate Serum Biomarkers of Doxorubicin-Induced Cardiotoxicity in Pediatric Acute Lymphoblastic Leukemia: Results of Nanoparticle-Capture Mass SpectrometryManuscript (preprint) (Other academic)
  • 298.
    Tamburro, Davide
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Colloidal/Solid Phase Extraction (C/S PE) Methods Based on Hydrogel Nanoparticles, Titanium dioxide microparticles and Empore Membranes Applied to Biological and Environmental Matrices2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of the work described in this thesis was to create and develop novel technologies in order to overcome barriers and hurdles that analytical chemistry faces focusing on sample extraction. In paper I dye containing amine groups (e.g. Acid Black 48, Remazol Brilliant Blue R) were coupled to NIPA/Acrylic acid (AAc) particles by condensation of the amine group and the carboxylic group. The high affinity between dyes and proteins allow for fast kinetics and complete depletion of the supernatant and protection of the captured analyte from enzymatic degradation. The ability of particles to capture and concentrate analytes was tested against a panel of low abundance, labile tumor relevant biomarkers and in serum. Results indicate that the nanoparticles increased the sensitivity limit of mass spectrometry analysis and that the dye based baits have extremely high affinity for the target analytes so that particles capture all the analyte present in solution. Biomarker harvesting nanoparticles may be useful for discovery of novel diagnostic analytes, can increase the sensitivity of detection for analytical methods such as immunoassays and MS, and protect labile biomarkers from degradation during collection, shipment and storage. In paper II and paper III, applications of hydrogel nanoparticles to serum samples from cancer patients are reported. Hydrogel nanoparticles were integrated in a mass spectrometry based workflow for the discovery of candidate biomarkers. Lists of candidate biomarkers were identified that are under verification and validation. In paper IV and V hydrogel nanoparticles functionalized with dyes, were employed to increase the sensitivity of diagnostic test for Lyme disease and to detect human growth hormone (hGH) in urine samples. In paper VI, titanium dioxide (TiO2) microparticles were used to pack fused silica capillary column and used to capture and enrich phosphopeptides in vitreous samples. In paper VII, Empore disk membranes were used to capture organophosphates (OPEs) flame retardant from air samples. Empore disk membranes were used as on- line extraction followed by reverse phase liquid chromatography tandem mass spectrometry (RPLC-MS/MS) analysis. Optimized “geometry” settings were used to strip semi volatile and volatile compounds from C8 membrane. This novel design allowed for a better analyte focusing in the HPLC column, reduced the volume of the organic solvent employed for the extraction and the analysis time, and eliminated sample contamination, and loss of analyte.

  • 299.
    Tamburro, Davide
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Multifunctional core-shell nanoparticles amplify sensitivity for low abundance biomarkers.Manuscript (preprint) (Other academic)
  • 300.
    Tamburro, Davide
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Fredolini, Claudia
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Espina, Virginia
    Douglas, Temple A.
    Ranganathan, Adarsh
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Zhou, Weidong
    Russo, Paul
    Espina, Benjamin H.
    Muto, Giovanni
    Petricoin, Emanuel F., III
    Liotta, Lance A.
    Luchini, Alessandra
    Multifunctional Core-Shell Nanoparticles: Discovery of Previously Invisible Biomarkers2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 47, p. 19178-19188Article in journal (Refereed)
    Abstract [en]

    Many low-abundance biomarkers for early detection of cancer and other diseases are invisible to mass spectrometry because they exist in body fluids in very low concentrations, are masked by high-abundance proteins such as albumin and immunoglobulins, and are very labile. To overcome these barriers, we created porous, buoyant, core-shell hydrogel nanoparticles containing novel high affinity reactive chemical baits for protein and peptide harvesting, concentration, and preservation in body fluids. Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles were functionalized with amino-containing dyes via zero-length cross-linking amidation reactions. Nanoparticles functionalized in the core with 17 different (12 chemically novel) molecular baits showed preferential high affinities (K(D) < 10(-11) M) for specific low-abundance protein analytes. A poly(N-isopropylacrylamide-co-vinylsulfonic acid) shell was added to the core particles. This shell chemistry selectively prevented unwanted entry of all size peptides derived from albumin without hindering the penetration of non-albumin small proteins and peptides. Proteins and peptides entered the core to be captured with high affinity by baits immobilized in the core. Nanoparticles effectively protected interleukin-6 from enzymatic degradation in sweat and increased the effective detection sensitivity of human growth hormone in human urine using multiple reaction monitoring analysis. Used in whole blood as a one-step, in-solution preprocessing step, the nanoparticles greatly enriched the concentration of low-molecular weight proteins and peptides while excluding albumin and other proteins above 30 kDa; this achieved a 10,000-fold effective amplification of the analyte concentration, enabling mass spectrometry (MS) discovery of candidate biomarkers that were previously undetectable.

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