Biomedical subjects

Herbert H Hill

Publications and source records attributed to Herbert H Hill.

At least 19 recordsLinked to original sources

PubMed2006

Gas-phase chiral separations by ion mobility spectrometry.

This article introduces the concept of chiral ion mobility spectrometry (CIMS) and presents examples demonstrating the gas-phase separation of enantiomers of a wide range of racemates including pharmaceuticals, amino acids, and carbohydrates. CIMS is similar to traditional ion mobility spectrometry, where gas-phase ions, when subjected to a potential gradient, are separated at atmospheric pressure due to differences in their shapes and sizes. In addition to size and shape, CIMS separates ions based on their stereospecific interaction with a chiral gas. In order to achieve chiral discrimination by CIMS, an asymmetric environment was provided by doping the drift gas with a volatile chiral reagent. In this study (S)-(+)-2-butanol was used as a chiral modifier to demonstrate enantiomeric separations of atenolol, serine, methionine, threonine, methyl alpha-glucopyranoside, glucose, penicillamine, valinol, phenylalanine, and tryptophan from their respective racemic mixtures.

Amino Acids↗

PubMed2006

A small subsurface ion mobility spectrometer sensor for detecting environmental soil-gas contaminants.

A small subsurface ion mobility spectrometer (SS-IMS) was constructed and tested with several environmental contaminants to determine its potential for monitoring gaseous volatile organic compounds in the vadose zone. Trichloroethylene (TCE) and tetrachloroethylene (PCE) were detected and separated in IMS for the first time. Detection limits as low as 1 part per billion volume-to-volume (ppb(v)) were observed. Reduced mobility (K(0)) values were reported for 11 environmental contaminants. These data demonstrated the potential of ion mobility spectrometry as a viable technology for detecting and separating environmental soil-gas contaminants in the field, which may lead to a practical and simple approach for long-term monitoring of contaminated soils.

Environmental Monitoring↗

PubMed2006

Characterizing electrospray ionization using atmospheric pressure ion mobility spectrometry.

Reduced flow rate electrospray ionization has been proven to provide improved sensitivity, less background noise, and improved limits of detections for ESI-MS analysis. Miniaturizing the ESI source from conventional electrospray to microelectrospray and further down to nanoelectrospray has resulted in higher and higher sensitivity; however, when effects of flow rate were investigated for atmospheric pressure ESI-IMS using a nanospray emitter, a striking opposite result was observed. The general tendency we observed in ESI-IMS was that higher flow rate offered higher ion signal intensity throughout a variety of conditions investigated. Thus, further efforts were undertaken to rationalize these contradictory results. It is well accepted that decreased flow rate increases both ionization efficiency and transmission efficiency, thus improving ion signal in ESI-MS. However, our study revealed that decreased flow rate results in decreased ion signal because ion transfer is constant, no matter how flow rate changes in ESI-IMS. Since ion transfer is constant in atmospheric pressure ESI-IMS, ionization efficiency can be studied independently, which otherwise is not possible in ESI-MS in which both ionization efficiency and transmission efficiency vary as conditions alter. In this article, we present a systematic study of signal intensity and ionization efficiency at various experimental conditions using ESI-IMS and demonstrate the ionization efficiency as a function of flow rate, analyte concentration, and solvent composition.

Atmospheric Pressure↗

PubMed2006

Ion-neutral potential models in atmospheric pressure ion mobility time-of-flight mass spectrometry IM(tof)MS.

The ion mobilities and their respective masses of several classes of amines (primary, secondary, and tertiary) were measured by electrospray ionization atmospheric pressure ion mobility time-of-flight mass spectrometry IM(tof)MS. The experimental data obtained were comparatively analyzed by the one-temperature kinetic theory of Chapman-Enskog. Several theoretical models were used to estimate the collision cross-sections; they include the rigid-sphere, polarization-limit, 12-6-4, and 12-4 potential models. These models were investigated to represent the interaction potentials contained within the collision integral that occurs between the polyatomic ions and the neutral drift gas molecules. The effectiveness of these collision cross-section models on predicting the mobility of these amine ions was explored. Moreover, the effects of drift gas selectivity on the reduced-mass term and in the collision cross-section term was examined. Use of a series of drift gases, namely, helium, neon, argon, nitrogen, and carbon dioxide, made it possible to distinguish between mass effects and polarizability effects. It was found that the modified 12-4 potential that compensates for the center of charge not being at the same location as the centers of mass showed improved agreement over the other collision cross-section models with respect to experimental data.

Amines↗

PubMed2006

Detection of aqueous phase chemical warfare agent degradation products by negative mode ion mobility time-of-flight mass spectrometry [IM(tof)MS].

The use of negative ion monitoring mode with an atmospheric pressure ion mobility orthogonal reflector time-of-flight mass spectrometer [IM(tof)MS] to detect chemical warfare agent (CWA) degradation products from aqueous phase samples has been determined. Aqueous phase sampling used a traditional electrospray ionization (ESI) source for sample introduction and ionization. Certified reference materials (CRM) of CWA degradation products for the detection of Schedule 1, 2, or 3 toxic chemicals or their precursors as defined by the chemical warfare convention (CWC) treaty verification were used in this study. A mixture of six G-series nerve related CWA degradation products (EMPA, IMPA, EHEP, IHEP, CHMPA, and PMPA) and their related collision induced dissociation (CID) fragment ions (MPA and EPA) were found in each case to be clearly resolved and detected using the IM(tof)MS instrument in negative ion monitoring mode. Corresponding ions, masses, drift times, K(o) values, and signal intensities for each of the CWA degradation products are reported.

Chemical Warfare Agents↗

PubMed2006

Hadamard transform ion mobility spectrometry.

Traditionally, the spectrum acquired using ion mobility spectrometry (IMS) is an average of multiple experimental cycles. Each cycle is initiated by passing a short burst of ions into a drift tube containing a homogeneous electric field. Prior to starting the subsequent cycle, all ions in the system must arrive at the detector or spectral overlap may occur. To maximize resolution, the ion pulse admitted to the drift tube is small in relation to the total scan time with the unfortunate consequence of an inherently low duty cycle (approximately 1%). Offering an improved SNR through a 50% duty cycle, the Hadamard transform (HT) applied to ion mobility spectrometry represents a fresh alternative to signal-averaged data acquisition. Initial results from measurements of amphetamine and cytochrome c samples indicate a 2-10-fold increase in SNR for the HT-IMS technique with no reduction in resolution.

Journal Article↗

PubMed2006

Influence of cation adduction on the separation characteristics of flavonoid diglycoside isomers using dual gate-ion mobility-quadrupole ion trap mass spectrometry.

An electrospray ionization-dual gate-ion mobility-quadrupole ion trap mass spectrometer was used to evaluate the separation characteristics of isomeric flavonoid diglycosides adducted with sodium, potassium, and silver. This instrumental configuration allows ions to be selectively accumulated within the ion trap on the basis of their gas phase conformation prior to mass analysis. For the metal cations examined, silver produced the most compact adducts with flavonoid diglycosides. Listed in order of increasing size, the trend of flavonoid diglycoside ion-neutral cross sections adducted with Na+, K+, and Ag+ was narirutin < naringin < hesperidin < neohesperidin < rutin. To examine the separation contribution of the carbohydrate group, hesperetin, the aglycone of hesperidin, and neohesperin were compared to quercetin, the aglycone of rutin. Separation of the flavonoid diglycosides indicated that quercetin-derived diglycosides drifted longer than their hesperetin-derived isomers. Combined with the observed collision assisted dissociation (CAD) data, these findings suggest that carbohydrate moiety plays a significant role in both the separation and metal chelating characteristics of flavonoid diglycosides.

Cations↗

PubMed2005

Mass analysis of mobility-selected ion populations using dual gate, ion mobility, quadrupole ion trap mass spectrometry.

An electrospray ionization, dual gate, ion mobility, quadrupole ion trap mass spectrometer (ESI-DG-IM-QIT-MS) was constructed and evaluated for its ability to select mobility-filtered ions prior to mass analysis. While modification of the common signal-averaged ion mobility experiment was required, no modifications to the QIT were necessary. The dual gate scanning mode of operation was used to acquire mobility spectra, whereas the single mobility monitoring experiment selectively filtered ions for concentration and subsequent fragmentation within the QIT. Ion mobility separation of positively charged peptides and negatively charged carbohydrates, followed by MS fragmentation, was demonstrated. For a 1-min acquisition time, it was possible to obtain complete de novo sequence information for the examined peptides. Fragmentation of the negative carbohydrate chlorine adducts yielded ions characteristic of cross-ring and glycosidic bond cleavage. Previous unions of atmospheric pressure ion mobility and mass spectrometry have been limited in their ability to reproducibly obtain MSn data for mobility separation ions. The union of high-pressure ion mobility with quadrupole ion trap mass spectrometry presents the unique opportunity to obtain more detailed information regarding the chemistries of gas-phase ions.

Journal Article↗

PubMed2005

Detection of a chemical warfare agent simulant in various aerosol matrixes by ion mobility time-of-flight mass spectrometry.

For the first time, a traditional radioactive nickel (63Ni) beta emission ionization source for ion mobility spectrometry was employed with an atmospheric pressure ion mobility orthogonal reflector time-of-flight mass spectrometer (IM(tof)MS) to detect a chemical warfare agent (CWA) simulant from aerosol samples. Aerosol-phase sampling employed a quartz cyclonic chamber for sample introduction. The simulant reference material, which closely mimicked the characteristic chemical structure of CWAs as defined and described by Schedule 1, 2, or 3 of the Chemical Warfare Convention treaty verification, was used in this study. An overall elevation in arbitrary signal intensity of approximately 1.0 orders of magnitude was obtained by the progressive increase of the thermal AP-IMS temperature from 75 to 275 degrees C. A mixture of one G-type nerve simulant (dimethyl methylphosphonate (DMMP)) in four (water, kerosene, gasoline, diesel) matrixes was found in each case (AP-IMS temperature 75-275 degrees C) to be clearly resolved in less than 2.20 x 10(4) micros using the IM(tof)MS instrument. Corresponding ions, masses, drift times, K(o) values, and arbitrary signal intensities for each of the sample matrixes are reported for the CWA simulant DMMP.

Journal Article↗

PubMed2005

Separation of sodiated isobaric disaccharides and trisaccharides using electrospray ionization-atmospheric pressure ion mobility-time of flight mass spectrometry.

A series of isobaric disaccharide-alditols, four derived from O-linked glycoproteins, and select trisaccharides were rapidly resolved using tandem high resolution atmospheric pressure ion-mobility time-of-flight mass spectrometry. Electrospray ionization was used to create the gas-phase sodium adducts of each carbohydrate. Using this technique it was possible to separate up to three isobaric disaccharide alditols and three trisaccharides in the gas phase. Reduced mobility values and experimentally determined ion-neutral cross sections are reported for each sodium-carbohydrate complex. These studies demonstrated that ion mobility separations at atmospheric pressure can provide a high-resolution dimension for analysis of carbohydrate ions that is complementary to traditional mass spectral (m/z) ion analysis. Combining these independent principles for separation of ions provides a powerful new bioanalytical tool for the identification of isomeric carbohydrates.

Disaccharides↗

PubMed2004

Secondary electrospray ionization-ion mobility spectrometry for explosive vapor detection.

The unique capability of secondary electrospray ionization (SESI) as a nonradioactive ionization source to detect analytes in both liquid and gaseous samples was evaluated using aqueous solutions of three common military explosives: cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), nitroglycerin (NG) and pentaerythritol tetranitrate (PETN). The adducts formed between the compounds and their respective dissociation product, RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-), gave the most intense signal for the individual compound but were more sensitive to temperature than other species. These autoadducts were identified as RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-) and had maximum signal intensity at 137, 100, and 125 degrees C, respectively. The reduced mobility values of the three compounds were constant over the temperature range from 75 to 225 degrees C. The signal-to-noise ratios for RDX, NG, and PETN at 50 mg L(-1) in methanol-water were 340, 270, and 170, respectively, with a nominal noise of 8 +/- 2 pA. In addition to the investigation of autoadduct formation, the concept of doping the ionization source with nonvolatile adduct-forming agents was investigated and described for the first time. The SESI-IMS detection limit for RDX was 116 microg L(-1) in the presence of a traditional volatile chloride dopant and 5.30 microg L(-1) in the presence of a nonvolatile nitrate dopant. In addition to a lower detection limit, the nitrate dopant also produced a greater response sensitivity and a higher limit of linearity than did the traditional volatile chloride dopant.

Azetidines↗

PubMed2004

Electrospray ionization-ion mobility spectrometry: a rapid analytical method for aqueous nitrate and nitrite analysis.

This paper reports the first example of electrospray ionization (ESI) for the separation and detection of anions in aqueous solutions by ion mobility spectrometry (IMS). Standard solutions of arsenate, phosphate, sulfate, nitrate, nitrite, chloride, formate, and acetate were analyzed using ESI-IMS and distinct peak patterns and reduced mobility constants (K(0)) were observed for respective anions. Real world water samples were analyzed for nitrate and nitrite to determine the feasibility of using ESI-IMS as a rapid analytical method for monitoring nitrate and nitrite in water systems. The data showed satisfactory correlation between the measured value ([similar]0.16 ppm) and the reported maximum nitrate-nitrogen concentration (0.2 ppm) found in a local drinking water system. For on-site measurement applications, direct sample introduction and air as an alternate drift gas to nitrogen were evaluated. The identities of the nitrite and nitrate mobility peaks were verified by comparison of reduced mobility constants with mass identified nitrate and nitrite ions reported in literature. In the mixing ratio, a linear dynamic range of 3 orders of magnitude and instrument detection limits of 10 ppb for nitrate and 40 ppb for nitrite were obtained. The calibration curves showed r(2) value of 0.98 and slope of 0.06 for nitrate and r(2) value of 0.99 and slope of 0.11 for nitrite.

Environmental Monitoring↗

PubMed2004

Atmospheric pressure matrix-assisted laser desorption/ionization with analysis by ion mobility time-of-flight mass spectrometry.

The use of an atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) source was employed with an atmospheric pressure ion mobility spectrometer (APIMS) and an orthogonal acceleration reflector time-of-flight mass spectrometer (TOFMS) to analyze dipeptide and biogenic amine mixtures from a liquid glycerol 2,5-dihydroxybenzoic acid (DHB) matrix. Improved sensitivities were obtained by the addition of a localized electrical (corona) discharge in conjunction with the AP-MALDI source. Enhanced sample ionization efficiency created by this combination provided an overall elevation in signal intensity of approximately 1.3 orders in magnitude. Combinations of three dipeptides (Gly-Lys, Ala-Lys, and Val-Lys) and nine biogenic amines (dopamine, serotonin, B-phenylethylamine, tyramine, octopamine, histamine, tryptamine, spermidine, and spermine) were resolved in less than 18 ms. In many cases, reduced mobility constants (K(o)) were determined for these analytes for the first time. Ion mobility drift times, flight times, arbitrary signal intensities, and collision-induced dissociation (CID) fragmentation product signatures are reported for each of the samples.

Atmospheric Pressure↗

PubMed2003

Secondary ionization of chemical warfare agent simulants: atmospheric pressure ion mobility time-of-flight mass spectrometry.

For the first time, the use of a traditional ionization source for ion mobility spectrometry (radioactive nickel ((63)Ni) beta emission ionization) and three alternative ionization sources (electrospray ionization (ESI), secondary electrospray ionization (SESI), and electrical discharge (corona) ionization (CI)) were employed with an atmospheric pressure ion mobility orthogonal reflector time-of-flight mass spectrometer (IM(tof)MS) to detect chemical warfare agent (CWA) simulants from both aqueous- and gas-phase samples. For liquid-phase samples, ESI was used as the sample introduction and ionization method. For the secondary ionization (SESI, CI, and traditional (63)Ni ionization) of vapor-phase samples, two modes of sample volatilization (heated capillary and thermal desorption chamber) were investigated. Simulant reference materials, which closely mimic the characteristic chemical structures of CWA as defined and described by Schedule 1, 2, or 3 of the Chemical Warfare Convention treaty verification, were used in this study. A mixture of four G/V-type nerve simulants (dimethyl methylphosphonate, pinacolyl methylphosphonate, diethyl phosphoramidate, and 2-(butylamino)ethanethiol) and one S-type vesicant simulant (2-chloroethyl ethyl sulfide) were found in each case (sample ionization and introduction methods) to be clearly resolved using the IM(tof)MS method. In many cases, reduced mobility constants (K(o)) were determined for the first time. Ion mobility drift times, flight times, relative signal intensities, and fragmentation product signatures for each of the CWA simulants are reported for each of the methods investigated.

Journal Article↗

PubMed2003

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of lipids: ionization and prompt fragmentation patterns.

Ionization and prompt fragmentation patterns of triacylglycerols, phospholipids (PLs) and galactolipids were investigated using matrix-assisted laser desorption/ionization (MALDI). Positive ions of non-nitrogen-containing lipids appeared only in the sodiated form, while nitrogen-containing lipids were detected as both sodiated and protonated adducts. Lipids containing acidic hydroxyls were detected as multiple sodium adducts or deprotonated ions in the positive and negative modes, respectively, with the exception of phosphatidylcholines. The positive MALDI spectra of triacylglycerols contained prompt fragments equivalent to the loss of RCOO(-) from the neutral molecules. Prompt fragment ions [PL-polar head](+) were observed in the positive MALDI spectra of all phospholipids except phosphatidylcholines. The phosphatidylcholines produced only a minor positive fragment corresponding to the head group itself (m/z 184). Galactolipids did not undergo prompt fragmentation. Post-source decay (PSD) was used to examine the source of prompt fragments. PSD fragment patterns indicated that the lipid prompt fragment ions did not originate from the observed molecular ions (sodiated or protonated), and suggested that the prompt fragmentation followed the formation of highly unstable, probably protonated, precursor ions. Pathways leading to the formation of prompt fragment ions are proposed.

Galactolipids↗

PubMed2002

Rapid separation of phenylthiohydantoin amino acids: ambient pressure ion-mobility mass spectrometry (IMMS).

An electrospray ionization (ESI) ambient pressure ion-mobility spectrometer (APIMS) interfaced to an orthogonal reflector time-of-flight mass spectrometer (TOFMS) was evaluated for the first time as a detector for the identification of phenylthiohydantoin (PTH)-derivatized amino acids, the final products in the Edman sequencing process of peptides and proteins. The drift and flight times of the twenty common PTH amino acids were characterized by a well-defined 2-D mobility/mass spectral pattern. The combination of mobility/mass modes of analysis gave rise to a unique trend-line formation for the series of PTH amino acids. In addition, each PTH amino acid had a unique reduced mobility constant K(o), thus enabling the differentiation of all the amino acid derivatives including the PTH-leucine and PTH-isoleucine isomers. More importantly it was shown that it was possible to resolve a complete reference mixture of PTH amino acids in a single experimental run in less than 1 min. Detection limits for the PTH amino acids were found to range from 1.04 to 3.52 ng; indicating that the limits of detection were less than 17.0 pmol for all of the PTH amino acids.

Amino Acids↗

PubMed2002

Rapid screening of aqueous chemical warfare agent degradation products: ambient pressure ion mobility mass spectrometry.

The use of electrospray ionization ambient pressure ion mobility spectrometry with an orthogonal reflector time-of-flight mass spectrometer to analyze chemical warfare (CW) degradation products from aqueous environmental samples has been demonstrated. Certified reference materials of analytical standards for the detection of Schedule 1, 2, or 3 toxic chemicals or their precursors as defined by the chemical warfare convention treaty verification were used in this study. A combination of six G/V-type nerve and four S-type vesicant related CW agent degradation products were separated with baseline resolution by this instrumental technique. Analytical figures of merit for each CW degradation product were determined. In some cases, reduced mobility constants (K0) have been reported for the first time. linear response ranges for the selected CW degradation products were found to be generally approximately 2 orders of magnitude, where the overall dynamic response ranges were found to extend to 4 orders of magnitude. Limits of detection for five of the nine chemical products tested were found to be less than 1 ppm. To demonstrate the potential of this instrumental method with complex mixtures, four CW degradation products were separated and detected from a spiked Palouse River water sample in less than 1 min. Finally, a homologous series of n-alkylamines were used as baseline reference standards, producing a mobility/mass trend line to which the CW degradation products could be compared. Comparison of these products in this manner is expected to reduce the number of false positive/negative responses.

Biodegradation, Environmental↗

PubMed2002

Relationship between MALDI-TOF analysis of beta-CN f193-209 concentration and sensory evaluation of bitterness intensity of aged cheddar cheese.

An internal standard method was previously developed to measure the concentration of a synthetic bitter peptide, beta-CN f193-209, by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The objective of this study was to evaluate the relationship between beta-CN f193-209 concentration in an aqueous extract of aged Cheddar cheese and bitterness intensity of the cheese. Concentrations of beta-CN f193-209 in cheese extracts were determined by MALDI-TOF at 0, 120, 180, and 270 days. Trained panels evaluated the bitterness intensity of the cheeses at 180 and 270 days. Correlation coefficients between MALDI and sensory data at 180 and 270 days were 0.803 and 0.554, respectively. The decreased correlation may be due to the presence of other bitter peptides more responsible for bitterness at longer aging or the production of compounds that mask bitterness intensity.

Aminopeptidases↗