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Biomedical subjects

H H Hill

Publications and source records attributed to H H Hill.

At least 19 recordsLinked to original sources
PubMed2003

Structural analysis of phosphatidylcholines by post-source decay matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The utility of post-source decay (PSD) matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was investigated for the structural analysis of phosphatidylcholine (PC). PC did not produce detectable negative molecular ion from MALDI, but positive ions were observed as both [PC+H](+) and [PC+Na](+). The PSD spectra of the protonated PC species contained only one fragment corresponding to the head group (m/z 184), while the sodiated precursors produced many fragment ions, including those derived from the loss of fatty acids. The loss of fatty acid from the C-1 position (sn-1) of the glycerol backbone was favored over the loss of fatty acid from the C-2 position (sn-2). Ions emanating from the fragmentation of the head group (phosphocholine) included [PC+Na-59](+), [PC+Na-183](+) and [PC+Na-205](+), which corresponded to the loss of trimethylamine (TMA), non-sodiated choline phosphate and sodiated choline phosphate, respectively. Other fragments reflecting the structure of the head group were observed at m/z 183, 146 and 86. The difference in the fragmentation patterns for the PSD of [PC+Na](+) compared to [PC+H](+) is attributed to difference in the binding of Na(+) and H(+). While the proton binds to a negatively charged oxygen of the phosphate group, the sodium ion can be associated with several regions of the PC molecule. Hence, in the sodiated PC, intermolecular interaction of the negatively charged oxygen of the phosphate group, along with sodium association at multiple sites, can lead to a complex and characteristic ion fragmentation pattern. The preferential loss of sn-1 fatty acid group could be explained by the formation of an energetically favorable six-member ring intermediate, as apposed to the five-member ring intermediate formed prior to the loss of sn-2 fatty acid group.

Molecular Structure↗
PubMed2001

Electrospray ionization high-resolution ion mobility spectrometry for the detection of organic compounds, 1. Amino acids.

Our aim in this investigation was to demonstrate the potential of the high-resolution electrospray ionization ion mobility spectrometry (ESI-IMS) technique as an analytical separation tool in analyzing biomolecular mixtures to pursue astrobiological objectives of searching for the chemical signatures of life during an in-situ exploration of solar system bodies. Because amino acids represent the basic building blocks of life, we used common amino acids to conduct the first part of our investigation, which is being reported here, to demonstrate the feasibility of using the ESI-IMS technique for detection of the chemical signatures of life. The ion mobilities of common amino acids were determined by electrospray ionization ion mobility spectrometry using three different drift gases (N2, Ar, and CO2). We demonstrated that the selectivity can be vastly improved in ion mobility spectroscopy (IMS) in detecting organic molecules by using different drift gases. When a judicial choice of drift gas is made, a vastly improved separation of two different amino acid ions resulted. It was found that each of the studied amino acids could be uniquely identified from the others, with the exception of alanine and glycine, which were never separable by more then 0.1 ms. This unique identification is a result of the different polarizabilities of the various drift gases. In addition, a better separation was achieved by changing the drift voltage in successive experimental runs without significantly degrading the resolution. We also report the result of our analysis of liquid samples containing mixtures of amino acids.

Amino Acids↗
PubMed2001

Evaluation of opiate separation by high-resolution electrospray ionization-ion mobility spectrometry/mass spectrometry.

The separation of opiates and the primary metabolites was evaluated with ESI-IMS/MS. Seven opiate molecules were analyzed, and spectra were shown for each compound. The IMS separation of two isomers (morphine and norcodeine) was shown with baseline separation. Differences in the mobilities were found for the nonacetylated, monoacetylated, and biacetylated compounds. In this study, two primary findings are reported. First, IMS can easily separate metabolic isomers, and second, the two-dimensional separation capability of IMS/MS can be employed to confidently identify and separate both the opiates and metabolites. Although previous IMS studies have shown the separation of isomers, this is the first example to show the capability of IMS to separate metabolic isomers (within 70 s), a significant advantage in high-throughput screening for pharmacokinetic studies. Second, the monoacetylated and biacetylated compounds were found to form more compact ions for the sodium adducts in comparison to the protonated molecular ions. On the basis of the mobilities, information on structures and conformation can be deduced when sodium and protonated ions are compared.

Indicators and Reagents↗
PubMed2001

Analysis of plant phosphatidylcholines by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The use of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) for the quantitative determination of phospholipid (PL) molecular species has been problematic, due primarily to the formation of multiple signals (corresponding to the molecular ion and other adducts) for some classes of PL. For example, analysis of phosphatidylcholine (PC) yielded signals that corresponded to protonated and sodiated molecules in the MALDI spectrum. The resulting spectral overlap among various molecular species (e.g. [PC(16:0/18:2) + Na] and [PC(18:2/18:3)]) made it impossible to ascertain their relative amounts using this technique. Other spectral ambiguities existed among different structural isomers, such as PC(18:1/18:1) and PC(18:0/18:2). We determined that molecular species could be resolved by MALDI-TOFMS by first removing the polar head (e.g. phosphocholine) from the phospholipid to effect production of only the sodiated molecules of the corresponding diacylglycerols (DAGs). Analysis of the resulting spectrum allowed unequivocal determination of the molecular species profile of PC from potato tuber and soybean. Estimation of fatty acid composition based on the molecular species determined by MALDI-TOFMS analysis agreed with that from GC-FID analysis. Post-source decay (PSD) was used to resolve standard isomers of PC (e.g. 18:1/18:1 vs. 18:0/18:2). Our results indicated that PSD is a useful approach for resolving structural isomers of PL molecular species.

Chromatography, Gas↗
PubMed2001

Electrospray ionization with ambient pressure ion mobility separation and mass analysis by orthogonal time-of-flight mass spectrometry.

Rapid screening and identification of drug and other mixtures are possible using a novel ambient pressure high-resolution ion mobility (APIMS) orthogonal reflector time-of-flight mass spectrometer (TOFMS). Departing ions from the APIMS drift tube traversed a pressure interface between the APIMS and TOFMS where they were subjected to numerous gas collisions that could produce selective fragmentation. By increasing the accelerating field in the pressure interface region, the ions generated using water-cooled electrospray ionization (ESI) underwent collision-induced dissociation (CID). Mixtures of ESI ions were separated by APIMS based on their respective size-to-charge (s/z) ratios while CID and analysis of mass-to-charge (m/z) ratios occurred in the pressure interface and TOFMS. Product ions that were formed in this pressure interface region could be readily assigned to precursor ions by matching the mobility drift times. This process was demonstrated by the examination of a mixture of amphetamines and the resulting fragmentation patterns of the mobility-separated precursor ion species [M + H](+).

Amphetamines↗
PubMed2000

Separation of amino acids by ion mobility spectrometry.

The mobilities of the 20 common amino acids were determined by electrospray ionization ion mobility spectrometry. It was found that each amino acid had a different drift time and hence a different reduced mobility constant K0. This difference in drift time was less than 0.1 ms in many cases. With the instrument used in this study it would not be possible to resolve mixtures of some of the amino acids. It would however be possible to determine any single amino acid. In addition, the detection limits were determined for the 20 amino acids. They ranged from 50 to 700 pg. This indicates that the detection limits were less than 3 pmol for all of the amino acids and that many amino acids had detection limits less than 1 pmol.

Amino Acids↗
PubMed2000

Separation of isomeric peptides using electrospray ionization/high-resolution ion mobility spectrometry.

In this paper, the first examples of baseline separation of isomeric macromolecules by electrospray ionization/ion mobility spectrometry (ESI/IMS) at atmospheric pressure are presented. The behavior of a number of different isomeric peptides in the IMS was investigated using nitrogen as a drift gas. The IMS was coupled to a quadrupole mass spectrometer, which was used for identification and selective detection of the electrosprayed ions. The mobility data were used to determine their average collision cross sections. The gas-phase ions of isomeric peptides were found to have different collision cross sections. In all cases, doubly charged ions exhibited significantly (8-20%) larger collision cross sections than the respective singly charged species. The analysis of mixtures of the isomeric peptides clearly demonstrated the capability of IMS to separate gas-phase peptide ions due to small differences in their conformational structures, which cannot be determined by mass spectrometry. An actual resolving power of 80 was achieved for two doubly charged reversed sequenced pentapeptides. Baseline separation was provided for ions differing by only 2.5% in their measured collision cross sections; partial separation was shown for isomeric ions exhibiting differences as small as 1.1%.

Algorithms↗
PubMed2000

Secondary electrospray ionization ion mobility spectrometry/mass spectrometry of illicit drugs.

A secondary electrospray ionization (SESI) method was developed as a nonradioactive ionization source for ion mobility spectrometry (IMS). This SESI method relied on the gas-phase interaction between charged particles created by electrospray ionization (ESI) and neutral gaseous sample molecules. Mass spectrometry (MS) was used as the detection method after ion mobility separation for ion identification. Preliminary investigations focussed on understanding the ionization process of SESI. The performance of ESI-IMS and SESI-IMS for illicit drug detection was evaluated by determining the analytical figures of merit. In general, SESI had a higher ionization efficiency for small volatile molecules compared with the electrospray method. The potential of developing a universal interface for both GC- and LC-MS with an addition stage of mobility separation was demonstrated.

Electrochemistry↗
PubMed1999

Atmospheric pressure ion mobility spectrometry of protonated and sodiated peptides.

A number of peptides were studied with electrospray ionization--ion mobility spectrometry/mass spectrometry (ESI-IMS/MS). The ion mobility data were used to calculate the average collision cross sections of the different detected peptide ions in the nitrogen drift gas. By comparing the cross sections of related ions, structural information about the most probable location of the charge and the gas-phase ion conformations was deduced. For bradykinin and kemptide, a significant mobility difference between protonated and sodiated species (where sodium replaced a proton in singly and doubly charged peptides) was demonstrated. Surprisingly, the doubly charged sodiated peptides had a smaller collision cross section than the doubly charged protonated ones leading to the conclusion that the gas-phase conformations of these ions are different with respect to intramolecular interactions.

Angiotensin II↗
PubMed1998

Gas chromatography.

This review of the fundamental developments in gas chromatography (GC) includes articles published from 1996 and 1997 and an occasional citation prior to 1996. The literature was reviewed principally using CA Selects for Gas Chromatography from Chemical Abstracts Service, and some significant articles from late 1997 may be missing from the review. In addition, the online SciSearch Database (Institute for Scientific Information) capability was used to abstract review articles or books. As with the prior recent reviews, emphasis has been given to the identification and discussion of selected developments, rather than a presentation of a comprehensive literature search, now available widely through computer-based resources. During the last two years, several themes emerged from a review of the literature. Multidimensional gas chromatography has undergone transformation encompassing a broad range of activity, including attempts to establish methods using chromatographic principles rather than a totally empirical approach. Another trend noted was a comparatively large effort in chromatographic theory through modeling efforts; these presumably became resurgent with inexpensive and powerful computing tools. Finally, an impressive level of activity was noted through the themes highlighted in this review, and this was particularly true with detectors and field instruments.

Chemistry Techniques, Analytical↗
PubMed1993

Quantification of mammalian lignans in biological fluids using gas chromatography with ion mobility detection.

A method is presented to quantify selected mammalian lignans in human physiological fluids by gas chromatography (GC) coupled with ion mobility spectrometry (IMS). The use of IMS following GC permitted the selective and sensitive measurement of 2,3-bis(3-hydroxybenzyl)butane-1,4-diol (i.e., enterodiol) and trans-2,3-bis(3-hydroxybenzyl)-gamma-butyrolactone (i.e., enterolactone) concentrations in urine and plasma following dietary supplementation with whole wheat/flaxseed bread high in mammalian lignan precursors. Following six weeks of flaxseed feeding, urinary and plasma levels of enterodiol and enterolactone were elevated, exceeding the amounts found at baseline by a factor of 3-5. The approach to mammalian lignan methodology presented herein provides novel analytical phytochemical procedures for assessing the impact of lignan consumption in human health and disease.

4-Butyrolactone↗
PubMed1990

Ion mobility detection of polydimethylsilicone oligomers following supercritical fluid chromatographic separation.

A mixture of polydimethylsilicones (Dow Corning 200), average molecular weight 2000 a.m.u., was separated by simultaneous density and temperature-programmed supercritical fluid chromatography and detected by ion mobility detection. Ion mobility spectra were captured by Fourier transform ion mobility spectrometry. Using information from these spectra it was possible to selectively detect a single compound in the complex mixture. A detector temperature investigation demonstrated that, for the efficient transfer of high-molecular-weight compounds from the column to the detector, the interface to the detector must be heated. Using a 50 microns I.D. column, a Guthrie-type restrictor and a detection temperature of 250 degrees C, as many as 70 oligomers were separated and detected.

Chromatography, High Pressure Liquid↗
PubMed1990

Subcutaneous infusions for control of cancer symptoms.

Continuous subcutaneous infusions offer a safe, simple, effective alternative to intravenous or intramuscular injections when oral medications cannot be used. They are extremely useful for cancer patients suffering from pain, vomiting, seizures, and other symptoms. Hydromorphone or morphine may be combined with metoclopramide, methotrimeprazine, or haloperidol (in D5W only), in the same pump to control both pain and nausea. Seizures can be controlled by subcutaneous infusion of phenobarbital or midazolam. If proper doses are prescribed and skin irritation is watched for, they can be used safely in the patient's home.

Analgesics↗
PubMed1989

Preliminary investigation of ion mobility spectrometry after capillary electrophoretic introduction.

Using standard capillary electrophoretic and ion mobility methods, several electrospray interface designs were investigated for the capillary electrophoretic introduction of samples into the ion mobility spectrometer. Of the interfaces investigated, the flow assisted interface and the direct coupled interface showed the most promise. These preliminary experiments were encouraging. The ion mobility spectrometer coupled with a capillary electrophoretic introduction system operated with excellent separation efficiency and ion mobility reproducibility. Using tetrabutylammonium iodide, the number of theoretical plates for the spectrometer was calculated to be 3.10(3) and reduced mobilities were found to be reproducible with a relative standard deviation of 1.43%. Because of the desire to hold the spectrometer as hot as possible, the solvent would often vaporize in the interface, creating an unstable spray and inhomogeneities in the electrophoretic field. More work is needed to improve the spray process which contributed to the overall noise of the system and to eliminate the phenomenon of solvent vaporization which limited the reproducibility of electrophoretic migration times.

Electrophoresis↗
PubMed1989

Evaluation of direct axial sample introduction for ion mobility detection after capillary gas chromatography.

An ion mobility detector has been designed and constructed for direct axial interfacing with capillary gas chromatography. The principle advantages of this detector were the following: (1) Direct concentric introduction of the capillary column into the ionization region, eliminating peak broadening in the transfer line and improving the efficiency with which neutral molecules were swept from the detector. (2) A variable capillary insertion distance, providing a sensitivity/resolution interplay that could be modified in response to the needs of the assay. (3) An inert gas flow external to the drift cylinder, preventing atmospheric impurities from infiltrating the ultratrace detector. Qualitative and quantitative capabilities of the detector were evaluated using standard preparations of n-hexyl ether.

Chromatography, Gas↗