Tandem Mass Spectrometry

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Michael H. Gelb - One of the best experts on this subject based on the ideXlab platform.

  • taiwan national newborn screening program by Tandem Mass Spectrometry for mucopolysaccharidoses types i ii and vi
    The Journal of Pediatrics, 2019
    Co-Authors: Minju Chan, Michael H. Gelb, Hsuanchieh Liao, Chihkuang Chuang, Meiying Liu, Hsiaojan Chen, Shumin Kao, Hsiangyu Lin, Youhsin Huang, Arun Kumar
    Abstract:

    Objective To evaluate the initial cutoff values, rates of screen positives, and genotypes for the large-scale newborn screening program for multiple mucopolysaccharidoses (MPS) in Taiwan. Study design More than 100 000 dried blood spots were collected consecutively as part of the national Taiwan newborn screening programs. Enzyme activities were measured by Tandem Mass Spectrometry from dried blood spot punches. Genotypes were obtained when a second newborn screening specimen again had a decreased enzyme activity. Additional clinical evaluation was then initiated based on enzyme activity and/or genotype. Results Molecular genetic analysis for cases with low enzyme activity revealed 5 newborns with pathogenic alpha-L-iduronidase mutations, 3 newborns with pathogenic iduronate-2-sulfatase mutations, and 1 newborn was a carrier of an arylsulfatase B mutation. Several variants of unknown pathogenic significance were also identified, most likely causing pseudodeficiency. Conclusions The highly robust Tandem Mass Spectrometry-based enzyme assays for MPS-I, MPS-II, and MPS-VI allow for high-throughput newborn screening for these lysosomal storage disorders. Optimized cutoff values combined with second tier testing could largely eliminate false-positive results. Accordingly, newborn screening for these lysosomal storage disorders is possible.

  • improved reagents for newborn screening of mucopolysaccharidosis types i ii and vi by Tandem Mass Spectrometry
    Analytical Chemistry, 2014
    Co-Authors: Naveen Kumar Chennamaneni, František Tureček, Ronald C Scott, Arun Kumar, Mariana Barcenas, Zdenek Spacil, Michael H. Gelb
    Abstract:

    Tandem Mass Spectrometry for the multiplex and quantitative analysis of enzyme activities in dried blood spots on newborn screening cards has emerged as a powerful technique for early assessment of lysosomal storage diseases. Here we report the design and process-scale synthesis of substrates for the enzymes α-l-iduronidase, iduronate-2-sulfatase, and N-acetylgalactosamine-4-sulfatase that are used for newborn screening of mucopolysaccharidosis types I, II, and VI. The products contain a bisamide unit that is hypothesized to readily protonate in the gas phase, which improves detection sensitivity by Tandem Mass Spectrometry. The products contain a benzoyl group, which provides a useful site for inexpensive deuteration, thus facilitating the preparation of internal standards for the accurate quantification of enzymatic products. Finally, the reagents are designed with ease of synthesis in mind, thus permitting scale-up preparation to support worldwide newborn screening of lysosomal storage diseases. The ne...

  • direct multiplex assay of enzymes in dried blood spots by Tandem Mass Spectrometry for the newborn screening of lysosomal storage disorders
    Journal of Inherited Metabolic Disease, 2006
    Co-Authors: Michael H. Gelb, František Tureček, Ron C Scott, Nestor A Chamoles
    Abstract:

    Tandem Mass Spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in rehydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using Tandem Mass Spectrometry with the aid of Mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann-Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid alpha-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10-12 individuals with the lysosomal storage disorder, the Tandem Mass Spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of approximately 1000 dried blood spots per day. Summary We have developed Tandem Mass Spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a high-throughput manner appropriate for newborn screening laboratories.

  • direct multiplex assay of enzymes in dried blood spots by Tandem Mass Spectrometry for the newborn screening of lysosomal storage disorders
    Journal of Inherited Metabolic Disease, 2006
    Co-Authors: Michael H. Gelb, František Tureček, Ron C Scott, Nestor A Chamoles
    Abstract:

    Tandem Mass Spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in rehydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using Tandem Mass Spectrometry with the aid of Mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann–Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid α-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10–12 individuals with the lysosomal storage disorder, the Tandem Mass Spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of ∼1000 dried blood spots per day. Summary We have developed Tandem Mass Spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a high-throughput manner appropriate for newborn screening laboratories.

Nestor A Chamoles - One of the best experts on this subject based on the ideXlab platform.

  • direct multiplex assay of enzymes in dried blood spots by Tandem Mass Spectrometry for the newborn screening of lysosomal storage disorders
    Journal of Inherited Metabolic Disease, 2006
    Co-Authors: Michael H. Gelb, František Tureček, Ron C Scott, Nestor A Chamoles
    Abstract:

    Tandem Mass Spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in rehydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using Tandem Mass Spectrometry with the aid of Mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann-Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid alpha-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10-12 individuals with the lysosomal storage disorder, the Tandem Mass Spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of approximately 1000 dried blood spots per day. Summary We have developed Tandem Mass Spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a high-throughput manner appropriate for newborn screening laboratories.

  • direct multiplex assay of enzymes in dried blood spots by Tandem Mass Spectrometry for the newborn screening of lysosomal storage disorders
    Journal of Inherited Metabolic Disease, 2006
    Co-Authors: Michael H. Gelb, František Tureček, Ron C Scott, Nestor A Chamoles
    Abstract:

    Tandem Mass Spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in rehydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using Tandem Mass Spectrometry with the aid of Mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann–Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid α-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10–12 individuals with the lysosomal storage disorder, the Tandem Mass Spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of ∼1000 dried blood spots per day. Summary We have developed Tandem Mass Spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a high-throughput manner appropriate for newborn screening laboratories.

Christopher M. Benton - One of the best experts on this subject based on the ideXlab platform.

  • liquid chromatography Tandem Mass Spectrometry of porphyrins and porphyrinogens in biological materials separation and identification of interfering poly ethylene glycol by travelling wave ion mobility Spectrometry Tandem Mass Spectrometry
    Biomedical Chromatography, 2013
    Co-Authors: Christopher M. Benton, Caje Moniz, Donald J. L. Jones
    Abstract:

    Biological and clinical samples for porphyrin and porphyrinogen analyses by liquid chromatography–Tandem Mass Spectrometry (LC-MS/MS) are often contaminated with poly(ethylene)glycol (PEG), which complicates the interpretation of Mass spectra and characterisation of new porphyrin metabolites. Two contaminating PEG molecules (m/z 833 and m/z 835) were completely separated from uroporphyrin I (m/z 831) by travelling wave ion mobility Spectrometry and characterised by Tandem Mass Spectrometry. One of the PEG species (m/z 835) also co-eluted with uroporphyrinogen I (m/z 837) and was unresolvable by travelling wave ion mobility Spectrometry/MS, therefore contaminating the MS/MS Mass spectra owing to isotope distribution. These PEG species, with the [M + H]+ ions at m/z at 833 and/or m/z 835, co-eluted with uroporphyrin I and uroporphyrinogen I by LC-MS/MS and could be wrongly identified as uroporphomethenes. Copyright © 2013 John Wiley & Sons, Ltd.

  • porphyrinogen fragmentation profiles by ultra high performance liquid chromatography electrospray ionisation Tandem Mass Spectrometry
    Rapid Communications in Mass Spectrometry, 2011
    Co-Authors: Christopher M. Benton, Caje Moniz, Chang Kee Lim, Donald J. L. Jones
    Abstract:

    An ultra-high-performance liquid chromatography/electrospray ionisation Tandem Mass Spectrometry system is described for the separation and characterisation of uroporphyrinogen, heptacarboxylic acid porphyrinogen, hexacarboxylic acid porphyrinogen, pentacarboxylic acid porphyrinogen and coproporphyrinogen. The separation was carried out on a 100 mm × 2.1 mm Thermo-Hypersil BDS column (2.4 µm average particle size) by gradient elution with a mixture of acetonitrile, methanol and 1 mol/L aqueous ammonium acetate buffer, pH 5.16, as eluent. The fragmentation pattern of each compound was established by collision-induced dissociation Tandem Mass Spectrometry. The most characteristic fragmentation was ring opening at one of the four methylene bridges of the protonated porphyrinogen molecule followed by further cleavages of methylene bridges linking the four pyrrole rings at various points to give product ions with methylenepyrrolenine, methylene-dipyrrolenine and methylene-tripyrrolenine structures.

  • Porphyrinogen fragmentation profiles by ultra-high-performance liquid chromatography/electrospray ionisation Tandem Mass Spectrometry.
    Rapid Communications in Mass Spectrometry, 2011
    Co-Authors: Christopher M. Benton, Caje Moniz, Donald J. L. Jones
    Abstract:

    An ultra-high-performance liquid chromatography/electrospray ionisation Tandem Mass Spectrometry system is described for the separation and characterisation of uroporphyrinogen, heptacarboxylic acid porphyrinogen, hexacarboxylic acid porphyrinogen, pentacarboxylic acid porphyrinogen and coproporphyrinogen. The separation was carried out on a 100 mm × 2.1 mm Thermo-Hypersil BDS column (2.4 µm average particle size) by gradient elution with a mixture of acetonitrile, methanol and 1 mol/L aqueous ammonium acetate buffer, pH 5.16, as eluent. The fragmentation pattern of each compound was established by collision-induced dissociation Tandem Mass Spectrometry. The most characteristic fragmentation was ring opening at one of the four methylene bridges of the protonated porphyrinogen molecule followed by further cleavages of methylene bridges linking the four pyrrole rings at various points to give product ions with methylenepyrrolenine, methylene-dipyrrolenine and methylene-tripyrrolenine structures.

Donald J. L. Jones - One of the best experts on this subject based on the ideXlab platform.

  • liquid chromatography Tandem Mass Spectrometry of porphyrins and porphyrinogens in biological materials separation and identification of interfering poly ethylene glycol by travelling wave ion mobility Spectrometry Tandem Mass Spectrometry
    Biomedical Chromatography, 2013
    Co-Authors: Christopher M. Benton, Caje Moniz, Donald J. L. Jones
    Abstract:

    Biological and clinical samples for porphyrin and porphyrinogen analyses by liquid chromatography–Tandem Mass Spectrometry (LC-MS/MS) are often contaminated with poly(ethylene)glycol (PEG), which complicates the interpretation of Mass spectra and characterisation of new porphyrin metabolites. Two contaminating PEG molecules (m/z 833 and m/z 835) were completely separated from uroporphyrin I (m/z 831) by travelling wave ion mobility Spectrometry and characterised by Tandem Mass Spectrometry. One of the PEG species (m/z 835) also co-eluted with uroporphyrinogen I (m/z 837) and was unresolvable by travelling wave ion mobility Spectrometry/MS, therefore contaminating the MS/MS Mass spectra owing to isotope distribution. These PEG species, with the [M + H]+ ions at m/z at 833 and/or m/z 835, co-eluted with uroporphyrin I and uroporphyrinogen I by LC-MS/MS and could be wrongly identified as uroporphomethenes. Copyright © 2013 John Wiley & Sons, Ltd.

  • porphyrinogen fragmentation profiles by ultra high performance liquid chromatography electrospray ionisation Tandem Mass Spectrometry
    Rapid Communications in Mass Spectrometry, 2011
    Co-Authors: Christopher M. Benton, Caje Moniz, Chang Kee Lim, Donald J. L. Jones
    Abstract:

    An ultra-high-performance liquid chromatography/electrospray ionisation Tandem Mass Spectrometry system is described for the separation and characterisation of uroporphyrinogen, heptacarboxylic acid porphyrinogen, hexacarboxylic acid porphyrinogen, pentacarboxylic acid porphyrinogen and coproporphyrinogen. The separation was carried out on a 100 mm × 2.1 mm Thermo-Hypersil BDS column (2.4 µm average particle size) by gradient elution with a mixture of acetonitrile, methanol and 1 mol/L aqueous ammonium acetate buffer, pH 5.16, as eluent. The fragmentation pattern of each compound was established by collision-induced dissociation Tandem Mass Spectrometry. The most characteristic fragmentation was ring opening at one of the four methylene bridges of the protonated porphyrinogen molecule followed by further cleavages of methylene bridges linking the four pyrrole rings at various points to give product ions with methylenepyrrolenine, methylene-dipyrrolenine and methylene-tripyrrolenine structures.

  • Porphyrinogen fragmentation profiles by ultra-high-performance liquid chromatography/electrospray ionisation Tandem Mass Spectrometry.
    Rapid Communications in Mass Spectrometry, 2011
    Co-Authors: Christopher M. Benton, Caje Moniz, Donald J. L. Jones
    Abstract:

    An ultra-high-performance liquid chromatography/electrospray ionisation Tandem Mass Spectrometry system is described for the separation and characterisation of uroporphyrinogen, heptacarboxylic acid porphyrinogen, hexacarboxylic acid porphyrinogen, pentacarboxylic acid porphyrinogen and coproporphyrinogen. The separation was carried out on a 100 mm × 2.1 mm Thermo-Hypersil BDS column (2.4 µm average particle size) by gradient elution with a mixture of acetonitrile, methanol and 1 mol/L aqueous ammonium acetate buffer, pH 5.16, as eluent. The fragmentation pattern of each compound was established by collision-induced dissociation Tandem Mass Spectrometry. The most characteristic fragmentation was ring opening at one of the four methylene bridges of the protonated porphyrinogen molecule followed by further cleavages of methylene bridges linking the four pyrrole rings at various points to give product ions with methylenepyrrolenine, methylene-dipyrrolenine and methylene-tripyrrolenine structures.

František Tureček - One of the best experts on this subject based on the ideXlab platform.

  • improved reagents for newborn screening of mucopolysaccharidosis types i ii and vi by Tandem Mass Spectrometry
    Analytical Chemistry, 2014
    Co-Authors: Naveen Kumar Chennamaneni, František Tureček, Ronald C Scott, Arun Kumar, Mariana Barcenas, Zdenek Spacil, Michael H. Gelb
    Abstract:

    Tandem Mass Spectrometry for the multiplex and quantitative analysis of enzyme activities in dried blood spots on newborn screening cards has emerged as a powerful technique for early assessment of lysosomal storage diseases. Here we report the design and process-scale synthesis of substrates for the enzymes α-l-iduronidase, iduronate-2-sulfatase, and N-acetylgalactosamine-4-sulfatase that are used for newborn screening of mucopolysaccharidosis types I, II, and VI. The products contain a bisamide unit that is hypothesized to readily protonate in the gas phase, which improves detection sensitivity by Tandem Mass Spectrometry. The products contain a benzoyl group, which provides a useful site for inexpensive deuteration, thus facilitating the preparation of internal standards for the accurate quantification of enzymatic products. Finally, the reagents are designed with ease of synthesis in mind, thus permitting scale-up preparation to support worldwide newborn screening of lysosomal storage diseases. The ne...

  • direct multiplex assay of enzymes in dried blood spots by Tandem Mass Spectrometry for the newborn screening of lysosomal storage disorders
    Journal of Inherited Metabolic Disease, 2006
    Co-Authors: Michael H. Gelb, František Tureček, Ron C Scott, Nestor A Chamoles
    Abstract:

    Tandem Mass Spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in rehydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using Tandem Mass Spectrometry with the aid of Mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann-Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid alpha-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10-12 individuals with the lysosomal storage disorder, the Tandem Mass Spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of approximately 1000 dried blood spots per day. Summary We have developed Tandem Mass Spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a high-throughput manner appropriate for newborn screening laboratories.

  • direct multiplex assay of enzymes in dried blood spots by Tandem Mass Spectrometry for the newborn screening of lysosomal storage disorders
    Journal of Inherited Metabolic Disease, 2006
    Co-Authors: Michael H. Gelb, František Tureček, Ron C Scott, Nestor A Chamoles
    Abstract:

    Tandem Mass Spectrometry is currently used in newborn screening programmes to quantify the level of amino acids and acylcarnitines in dried blood spots for detection of metabolites associated with treatable diseases. We have developed assays for lysosomal enzymes in rehydrated dried blood spots in which a set of substrates is added and the set of corresponding enzymatic products are quantified using Tandem Mass Spectrometry with the aid of Mass-differentiated internal standards. We have developed a multiplex assay of the set of enzymes that, when deficient, cause the lysosomal storage disorders Fabry, Gaucher, Hurler, Krabbe, Niemann–Pick A/B and Pompe diseases. These diseases were selected because treatments are now available or expected to emerge shortly. The discovery that acarbose is a selective inhibitor of maltase glucoamylase allows the Pompe disease enzyme, acid α-glucosidase, to be selectively assayed in white blood cells and dried blood spots. When tested with dried blood spots from 40 unaffected individuals and 10–12 individuals with the lysosomal storage disorder, the Tandem Mass Spectrometry assay led to the correct identification of the affected individuals with 100% sensitivity. Many of the reagents needed for the new assays are commercially available, and those that are not are being prepared under Good Manufacturing Procedures for approval by the FDA. Our newborn screening assay for Krabbe disease is currently being put in place at the Wadsworth Center in New York State for the analysis of ∼1000 dried blood spots per day. Summary We have developed Tandem Mass Spectrometry for the direct assay of lysosomal enzymes in rehydrated dried blood spots that can be implemented for newborn screening of lysosomal storage disorders. Several enzymes can be analysed by a single method (multiplex analysis) and in a high-throughput manner appropriate for newborn screening laboratories.