Rapid Communications in Mass Spectrometry, May 21, 2013
To provide a simple one-step derivatization procedure for the analysis of a wide variety of amino... more To provide a simple one-step derivatization procedure for the analysis of a wide variety of amino acids in human hair by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). N,O-Bis(trimethylsilyl)trifluoroacetamide (BSTFA) derivatization is already widely used outside the IRMS community, is applicable to a variety of functional groups, and provides products that are common entries in mass spectral databases, thus simplifying compound identification. Method optimization and validation were performed on a mixture of ten standard amino acids found abundantly in human hair. The method was then applied to the analysis of scalp hair from six human subjects. The hair was washed, hydrolyzed with 6 M HCl, derivatized using BSTFA in acetonitrile and analyzed using gas chromatography (GC) with concurrent quadrupole and isotope ratio mass spectrometry (IRMS) detectors. The reproducibility for the δ(13)C measurements, including the derivatization procedure and GC/C/IRMS analysis, on a day-to-day comparison was between 0.19‰ and 0.35‰ (SD, N = 12), with an average standard deviation of 0.26‰. Because trimethylsilylation adds 3N carbon atoms (where N = # reactive protons) to each amino acid, the δ(13)C values for amino acid derivatives were corrected using a mass balance correction and the measured kinetic isotope effect (KIE). The KIE values ranged from 0.984 to 1.020. The procedure gave consistent δ(13)C values with precision similar to other derivatization methods for the range of sample sizes studied: 50-1000 µg of each amino acid. The method gave δ(13)C values consistent with the known literature values when applied to the analysis of amino acids in human hair.
Journal of the American Society for Mass Spectrometry, 2022
Research in natural products (NPs) has gained interest as drug developers turn to nature to comba... more Research in natural products (NPs) has gained interest as drug developers turn to nature to combat problems with drug resistance, drug delivery, and emerging diseases. Whereas NPs offer a tantalizing source of new pharmacologically active compounds, their structural complexity presents a challenge for analytical characterization and organic synthesis. Of particular concern is the characterization of cyclic-, polycyclic-, or macrocyclic compounds. One example of endogenous compounds as inspiration for NP development are cobalamins, like vitamin B12. An example of exogenous NPs is the class of macrolides that includes erythromycin. Both classes of macrocycles feature analogues with a range of modifications on their macrocyclic cores, but because of their cyclic nature, they are generally resistant to fragmentation by collision-induced dissociation (CID). In the present work, charge-transfer dissociation (CTD) was employed, with or without supplemental collisional activation, to produce radical-driven, high-energy fragmentation products of different macrocyclic precursors. With the assistance of collisional activation of CTnoD products, CTD frequently cleaved two covalent bonds within the macrocycle cores to reveal rich, informative spectra that helped identify sites of modification and resolve structural analogues. In a third example of macrocycle fragmentation, CTD enabled an impurity in a biological sample to be characterized as a cyclic polymer of nylon-6,6. In each example, CTD spectra are starkly different from CID and are highly reminiscent of other high-energy fragmentation techniques like extreme ultraviolet dissociative photoionization (XUV-DPI) and electron ionization-induced dissociation (EID). The results indicate that CTD-MS is a useful tool for the characterization of natural and synthetic macrocycles.
Energetics and efficiencies of collision-induced dissociation achieved during the mass acquisitio... more Energetics and efficiencies of collision-induced dissociation achieved during the mass acquisition scan in a quadrupole ion trap
L'invention porte sur un spectrometre de masse portable (10) comprenant une source d'ions... more L'invention porte sur un spectrometre de masse portable (10) comprenant une source d'ions (12), un detecteur d'ions (14) et un separateur d'ions passe-haut de type Loeb-Eiber comprenant un reseau de fils (28). Le reseau (28) peut avoir des premier et second ensembles (34, 36) de fils dans lesquels la distance entre des fils adjacents est inferieure au diametre de chacun des fils. Un generateur electrique (38) peut etre configure pour creer un courant electrique et alimenter en courant electrique le premier ensemble de fils (34) tandis que le second ensemble de fils (36) reste mis a la masse.
Abstract This work focuses on the application of charge transfer dissociation (CTD) to a mannuron... more Abstract This work focuses on the application of charge transfer dissociation (CTD) to a mannuronic acid oligomer with different extents of Na/H exchange. The goals were to determine if CTD could effectively characterize the oligomer and to investigate how Na/H exchanges impact the CTD fragmentation pathways of even a simple oligomer like mannuronic acid. CTD provided unique and unambiguous fragments that helped determine the 1-4-linkage pattern between core mannuronic acid residues. CTD of precursors with no Na/H exchange mainly had unambiguous product ions. However, CTD of precursor ions containing two or more Na/H exchanges increased the number of possible product ion identities and yielded many isobaric product ions and, hence, more ambiguity in spectral assignments. The use of 18O labelling on the reducing terminus helped resolve some isobaric interferences between A/X, and C/Z ions but created some nominal overlap with fragment ions containing Na/H exchanges. CTD spectra demonstrated that when three or more Na/H exchanges are present in the precursor, there are at least two main conformers of Na/H exchange sites: the first conformer contains three Na/H exchanges on adjacent sugars closest to the non-reducing terminus and a second conformer contains two adjacent Na/H exchanges on the reducing terminus. When four or five Na/H exchanges are present, the positions of the fourth and fifth sodium ions could not be confirmed, presumably because the isolated precursors contain a distribution of conformers with Na/H exchanges in different positions. In the absence of Na/H exchanges, He-CTD spectra provided rich structural information and very few ambiguous product ions. Therefore, until CTD is coupled to high-resolution mass spectrometers—which could readily resolve the ambiguity in most of the peak identities—precursors that contain the fewest possible number of Na/H exchanges will provide the most confident peak assignments and structural characterization.
An expedited field analysis method was developed for the determination of polychlorinated bipheny... more An expedited field analysis method was developed for the determination of polychlorinated biphenyls (PCBs) in soil matrices using a portable gas chromatography-mass spectrometry (GC-MS) instrument. Soil samples of approximately 0.5 g were measured with a portable scale and PCBs were extracted by headspace solid-phase microextraction (SPME) with a 100 µm polydimethylsiloxane (PDMS) fiber. Two milliliters of 0.2 M potassium permanganate and 0.5 mL of 6 M sulfuric acid solution were added to the soil matrices to facilitate the extraction of PCBs. The extraction was performed for 30 min at 100 ℃ in a portable heating block that was powered by a portable generator. The portable GC-MS instrument took less than 6 min per analysis and ran off an internal battery and helium cylinder. Six commercial PCB mixtures, Aroclor 1016, 1221, 1232, 1242, 1248, 1254, and 1260, could be classified based on the GC chromatograms and mass spectra. The detection limit of this method for Aroclor 1260 in soil ...
Phospholipid cations formed by electrospray ionization were subjected to excitation and fragmenta... more Phospholipid cations formed by electrospray ionization were subjected to excitation and fragmentation by a beam of 6 keV helium cations in a process termed charge transfer dissociation (CTD). The resulting fragmentation pattern in CTD is different from that of conventional collision-induced dissociation (CID), but analogous to that of metastable atom-activated dissociation (MAD) and electron-induced dissociation (EID). Like CID, CTD yields product ions indicative of acyl chain lengths and degrees of unsaturation in the fatty acyl moieties, but also provides additional structural diagnostic information, such as double bond position. Although CTD hasn't been tested on a larger lipid sample pool, the extent of structural information obtained demonstrates that CTD is a useful tool for lipid structure characterization, and a potentially useful tool in future lipidomics workflows. CTD is relatively unique in that it can produce a relatively strong series of 2+ product ions with enhanc...
Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source coupled to ... more Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source coupled to the Q Exactive Plus has been extensively used in untargeted mass spectrometry imaging (MSI) analyses of biological tissue sections. Although the Orbitrap is a high-resolution and accurate-mass (HRAM) mass analyzer, these attributes alone cannot be used for the reliable identification of unknown analytes observed in complex biological matrices. Spectral accuracy (SA) is the ability of the mass spectrometer to accurately measure the isotopic distributions which, when used with high mass measurement accuracy (MMA), can facilitate the elucidation of a single elemental composition. To investigate the effects of different ion populations on an Orbitrap's SA and MMA, a solution of caffeine, the tetrapeptide MRFA, and ultramark was analyzed using a Q Exactive Plus across eight distinct automatic gain control (AGC) targets. The same compounds from the same lot numbers were also individually a...
The combination of helium charge transfer dissociation mass spectrometry (He–CTD–MS) with ultrahi... more The combination of helium charge transfer dissociation mass spectrometry (He–CTD–MS) with ultrahigh performance liquid chromatography (UHPLC) is presented for the analysis of a complex mixture of acidic and neutral human milk oligosaccharides (HMOs). The research focuses on the identification of the monosaccharide sequence, the branching patterns, the sialylation/fucosylation arrangements, and the differentiation of isomeric oligosaccharides in the mixture. Initial studies first optimized the conditions for the UHPLC separation and the He–CTD–MS conditions. Results demonstrate that He–CTD is compatible with UHPLC timescales and provides unambiguous glycosidic and cross-ring cleavages from both the reducing and the nonreducing ends, which is not typically possible using collision-induced dissociation. He–CTD produces informative fragments, including 0,3An and 0,4An ions, which have been observed with electron transfer dissociation, electron detachment dissociation, and ultraviolet ph...
Charge transfer dissociation-mass spectrometry (CTD-MS) enables the differentiation of l- and d-e... more Charge transfer dissociation-mass spectrometry (CTD-MS) enables the differentiation of l- and d-epimers of Asp and isoASP amino acids in peptides.
Excel Spreadsheet contains all the retention times, retention indices, mass spectral peak abundan... more Excel Spreadsheet contains all the retention times, retention indices, mass spectral peak abundances and chromatography performance calculations.
Rapid Communications in Mass Spectrometry, May 21, 2013
To provide a simple one-step derivatization procedure for the analysis of a wide variety of amino... more To provide a simple one-step derivatization procedure for the analysis of a wide variety of amino acids in human hair by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). N,O-Bis(trimethylsilyl)trifluoroacetamide (BSTFA) derivatization is already widely used outside the IRMS community, is applicable to a variety of functional groups, and provides products that are common entries in mass spectral databases, thus simplifying compound identification. Method optimization and validation were performed on a mixture of ten standard amino acids found abundantly in human hair. The method was then applied to the analysis of scalp hair from six human subjects. The hair was washed, hydrolyzed with 6 M HCl, derivatized using BSTFA in acetonitrile and analyzed using gas chromatography (GC) with concurrent quadrupole and isotope ratio mass spectrometry (IRMS) detectors. The reproducibility for the δ(13)C measurements, including the derivatization procedure and GC/C/IRMS analysis, on a day-to-day comparison was between 0.19‰ and 0.35‰ (SD, N = 12), with an average standard deviation of 0.26‰. Because trimethylsilylation adds 3N carbon atoms (where N = # reactive protons) to each amino acid, the δ(13)C values for amino acid derivatives were corrected using a mass balance correction and the measured kinetic isotope effect (KIE). The KIE values ranged from 0.984 to 1.020. The procedure gave consistent δ(13)C values with precision similar to other derivatization methods for the range of sample sizes studied: 50-1000 µg of each amino acid. The method gave δ(13)C values consistent with the known literature values when applied to the analysis of amino acids in human hair.
Journal of the American Society for Mass Spectrometry, 2022
Research in natural products (NPs) has gained interest as drug developers turn to nature to comba... more Research in natural products (NPs) has gained interest as drug developers turn to nature to combat problems with drug resistance, drug delivery, and emerging diseases. Whereas NPs offer a tantalizing source of new pharmacologically active compounds, their structural complexity presents a challenge for analytical characterization and organic synthesis. Of particular concern is the characterization of cyclic-, polycyclic-, or macrocyclic compounds. One example of endogenous compounds as inspiration for NP development are cobalamins, like vitamin B12. An example of exogenous NPs is the class of macrolides that includes erythromycin. Both classes of macrocycles feature analogues with a range of modifications on their macrocyclic cores, but because of their cyclic nature, they are generally resistant to fragmentation by collision-induced dissociation (CID). In the present work, charge-transfer dissociation (CTD) was employed, with or without supplemental collisional activation, to produce radical-driven, high-energy fragmentation products of different macrocyclic precursors. With the assistance of collisional activation of CTnoD products, CTD frequently cleaved two covalent bonds within the macrocycle cores to reveal rich, informative spectra that helped identify sites of modification and resolve structural analogues. In a third example of macrocycle fragmentation, CTD enabled an impurity in a biological sample to be characterized as a cyclic polymer of nylon-6,6. In each example, CTD spectra are starkly different from CID and are highly reminiscent of other high-energy fragmentation techniques like extreme ultraviolet dissociative photoionization (XUV-DPI) and electron ionization-induced dissociation (EID). The results indicate that CTD-MS is a useful tool for the characterization of natural and synthetic macrocycles.
Energetics and efficiencies of collision-induced dissociation achieved during the mass acquisitio... more Energetics and efficiencies of collision-induced dissociation achieved during the mass acquisition scan in a quadrupole ion trap
L'invention porte sur un spectrometre de masse portable (10) comprenant une source d'ions... more L'invention porte sur un spectrometre de masse portable (10) comprenant une source d'ions (12), un detecteur d'ions (14) et un separateur d'ions passe-haut de type Loeb-Eiber comprenant un reseau de fils (28). Le reseau (28) peut avoir des premier et second ensembles (34, 36) de fils dans lesquels la distance entre des fils adjacents est inferieure au diametre de chacun des fils. Un generateur electrique (38) peut etre configure pour creer un courant electrique et alimenter en courant electrique le premier ensemble de fils (34) tandis que le second ensemble de fils (36) reste mis a la masse.
Abstract This work focuses on the application of charge transfer dissociation (CTD) to a mannuron... more Abstract This work focuses on the application of charge transfer dissociation (CTD) to a mannuronic acid oligomer with different extents of Na/H exchange. The goals were to determine if CTD could effectively characterize the oligomer and to investigate how Na/H exchanges impact the CTD fragmentation pathways of even a simple oligomer like mannuronic acid. CTD provided unique and unambiguous fragments that helped determine the 1-4-linkage pattern between core mannuronic acid residues. CTD of precursors with no Na/H exchange mainly had unambiguous product ions. However, CTD of precursor ions containing two or more Na/H exchanges increased the number of possible product ion identities and yielded many isobaric product ions and, hence, more ambiguity in spectral assignments. The use of 18O labelling on the reducing terminus helped resolve some isobaric interferences between A/X, and C/Z ions but created some nominal overlap with fragment ions containing Na/H exchanges. CTD spectra demonstrated that when three or more Na/H exchanges are present in the precursor, there are at least two main conformers of Na/H exchange sites: the first conformer contains three Na/H exchanges on adjacent sugars closest to the non-reducing terminus and a second conformer contains two adjacent Na/H exchanges on the reducing terminus. When four or five Na/H exchanges are present, the positions of the fourth and fifth sodium ions could not be confirmed, presumably because the isolated precursors contain a distribution of conformers with Na/H exchanges in different positions. In the absence of Na/H exchanges, He-CTD spectra provided rich structural information and very few ambiguous product ions. Therefore, until CTD is coupled to high-resolution mass spectrometers—which could readily resolve the ambiguity in most of the peak identities—precursors that contain the fewest possible number of Na/H exchanges will provide the most confident peak assignments and structural characterization.
An expedited field analysis method was developed for the determination of polychlorinated bipheny... more An expedited field analysis method was developed for the determination of polychlorinated biphenyls (PCBs) in soil matrices using a portable gas chromatography-mass spectrometry (GC-MS) instrument. Soil samples of approximately 0.5 g were measured with a portable scale and PCBs were extracted by headspace solid-phase microextraction (SPME) with a 100 µm polydimethylsiloxane (PDMS) fiber. Two milliliters of 0.2 M potassium permanganate and 0.5 mL of 6 M sulfuric acid solution were added to the soil matrices to facilitate the extraction of PCBs. The extraction was performed for 30 min at 100 ℃ in a portable heating block that was powered by a portable generator. The portable GC-MS instrument took less than 6 min per analysis and ran off an internal battery and helium cylinder. Six commercial PCB mixtures, Aroclor 1016, 1221, 1232, 1242, 1248, 1254, and 1260, could be classified based on the GC chromatograms and mass spectra. The detection limit of this method for Aroclor 1260 in soil ...
Phospholipid cations formed by electrospray ionization were subjected to excitation and fragmenta... more Phospholipid cations formed by electrospray ionization were subjected to excitation and fragmentation by a beam of 6 keV helium cations in a process termed charge transfer dissociation (CTD). The resulting fragmentation pattern in CTD is different from that of conventional collision-induced dissociation (CID), but analogous to that of metastable atom-activated dissociation (MAD) and electron-induced dissociation (EID). Like CID, CTD yields product ions indicative of acyl chain lengths and degrees of unsaturation in the fatty acyl moieties, but also provides additional structural diagnostic information, such as double bond position. Although CTD hasn't been tested on a larger lipid sample pool, the extent of structural information obtained demonstrates that CTD is a useful tool for lipid structure characterization, and a potentially useful tool in future lipidomics workflows. CTD is relatively unique in that it can produce a relatively strong series of 2+ product ions with enhanc...
Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source coupled to ... more Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source coupled to the Q Exactive Plus has been extensively used in untargeted mass spectrometry imaging (MSI) analyses of biological tissue sections. Although the Orbitrap is a high-resolution and accurate-mass (HRAM) mass analyzer, these attributes alone cannot be used for the reliable identification of unknown analytes observed in complex biological matrices. Spectral accuracy (SA) is the ability of the mass spectrometer to accurately measure the isotopic distributions which, when used with high mass measurement accuracy (MMA), can facilitate the elucidation of a single elemental composition. To investigate the effects of different ion populations on an Orbitrap's SA and MMA, a solution of caffeine, the tetrapeptide MRFA, and ultramark was analyzed using a Q Exactive Plus across eight distinct automatic gain control (AGC) targets. The same compounds from the same lot numbers were also individually a...
The combination of helium charge transfer dissociation mass spectrometry (He–CTD–MS) with ultrahi... more The combination of helium charge transfer dissociation mass spectrometry (He–CTD–MS) with ultrahigh performance liquid chromatography (UHPLC) is presented for the analysis of a complex mixture of acidic and neutral human milk oligosaccharides (HMOs). The research focuses on the identification of the monosaccharide sequence, the branching patterns, the sialylation/fucosylation arrangements, and the differentiation of isomeric oligosaccharides in the mixture. Initial studies first optimized the conditions for the UHPLC separation and the He–CTD–MS conditions. Results demonstrate that He–CTD is compatible with UHPLC timescales and provides unambiguous glycosidic and cross-ring cleavages from both the reducing and the nonreducing ends, which is not typically possible using collision-induced dissociation. He–CTD produces informative fragments, including 0,3An and 0,4An ions, which have been observed with electron transfer dissociation, electron detachment dissociation, and ultraviolet ph...
Charge transfer dissociation-mass spectrometry (CTD-MS) enables the differentiation of l- and d-e... more Charge transfer dissociation-mass spectrometry (CTD-MS) enables the differentiation of l- and d-epimers of Asp and isoASP amino acids in peptides.
Excel Spreadsheet contains all the retention times, retention indices, mass spectral peak abundan... more Excel Spreadsheet contains all the retention times, retention indices, mass spectral peak abundances and chromatography performance calculations.
Uploads
Papers by Glen Jackson