Richard A. Yost

Flavanone absorption after naringin, hesperidin, and citrus administration

Disposition of citrus flavonoids was evaluated after single oral doses of pure compounds (500 mg naringin and 500 mg hesperidin) and after multiple doses of combined grapefruit juice and orange juice and of once‐daily grapefruit. Cumulative urinary recovery indicated low bioavailability (<25%) of naringin and hesperidin. The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization‐collisionally activated dissociation tandem mass spectrometry (PCI‐CAD MS/MS). After juice administration, PCI‐CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives. These methoxyflavanones appear to be absorbed from juice. Absorbed citrus flavanones may undergo glucuronidation before urinary excretion.

Triple quadrupole mass spectrometry for direct mixture analysis and structure elucidation.

Abstract : The triple quadrupole mass spectrometer is shown to be a simple and highly efficient system for the observation of the fragmentation pattern of selected ions. The instrument consists of, in series, a CI/EI ion source, a quadrupole mass filter, an RF-only quadrupole collision chamber, a second mass filter, and an electron multiplier. The high sensitivity of the MS/MS technique with quadrupoles depends particularly on the highly efficient low energy collision-induced dissociation process in the strong focusing RF quadrupole field. Detection limits for methane and nitrobenzene of 10 to the minus 15 mole are shown. Analysis of a mixture of six components, including two isomers and an isobaric compound is presented. Chemical noise is virtually eliminated by the selection of both parent and fragment ion. An application of the system for structure elucidation is also described. (Author)

High Efficiency Collision-Induced Dissociation in an RF-Only Quadrupole.

Collision-induced dissociation (CID), when performed in an RF-only quadrupole is a highly efficient method of fragmenting ions. The low-energy (5-10 eV) CID process, may involve direct vibrational excitation by momentum transfer but in any case, is a very different process from the high energy (3-10 keV) electronic excitation CID process observed in MIKES and CAMS. Experimental results are presented which demonstrate the efficiency of CID fragmentation (up to 65%), the elimination of scattering losses, and the effects of varying such experimental parameters as choice and pressure of collision gas, ion velocity in the quadrupole, and quadrupole RF voltage and frequency. The appearance of the CID fragmentation spectra is roughly similar to 14 eV EI spectra. The results of digital simulation of ion trajectories in an RF-only quadrupole are presented. The correspondence between simulated and experimental results aids in the understanding of the quadrupole CID process. The high efficiency of the CID process in an RF-only quadrupole is significant in the development of a tandem quadrupole mass spectrometer for selected ion fragmentation studies.

Detection of pharmaceutical compounds in tissue by matrix-assisted laser desorption/ionization and laser desorption/chemical ionization tandem mass spectrometry with a quadrupole ion trap

A novel quadrupole ion trap mass spectrometer laser microprobe instrument with an external ionization source was constructed and used to investigate the matrix-assisted laser desorption/ionization (MALDI) detection of pharmaceutical compounds in intact tissue. In addition to MALDI, laser desorption coupled with chemical ionization (LD/CI) was investigated. MALDI, using 2,5-dihydroxybenezoic acid (DHB) as a matrix, was employed to detect the anticancer drug paclitaxel from a thin section of rat liver tissue which had been incubated in a solution of paclitaxel. The results of that experiment showed that the ability to perform tandem mass spectrometry (MS/MS) with the quadrupole ion trap was crucial in the identification of drug compounds at trace levels in the complex tissue matrix. MALDI MS/MS was then used to detect the presence of paclitaxel in a human ovarian tumor at a concentration of approximately 50 mg/kg. Finally, the drug spiperone was detected in incubated rat liver tissue at an approximate level of 25 mg/kg using LD/CI (no MALDI matrix). Again, the MS/MS capability of the quadrupole ion trap was crucial in the identification of the drug at trace levels in the complex tissue matrix.

Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard.

Mass spectrometric imaging (MSI) is an analytical technique used to determine the distribution of individual analytes within a given sample. A wide array of analytes and samples can be investigated by MSI, including drug distribution in rats, lipid analysis from brain tissue, protein differentiation in tumors, and plant metabolite distributions. Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization technique capable of desorbing and ionizing a large range of compounds, and it is the most common ionization source used in MSI. MALDI mass spectrometry (MS) is generally considered to be a qualitative analytical technique because of significant ion-signal variability. Consequently, MSI is also thought to be a qualitative technique because of the quantitative limitations of MALDI coupled with the homogeneity of tissue sections inherent in an MSI experiment. Thus, conclusions based on MS images are often limited by the inability to correlate ion signal increases with actual concentration increases. Here, we report a quantitative MSI method for the analysis of cocaine (COC) from brain tissue using a deuterated internal standard (COC-d(3)) combined with wide-isolation MS/MS for analysis of the tissue extracts with scan-by-scan COC-to-COC-d(3) normalization. This resulted in significant improvements in signal reproducibility and calibration curve linearity. Quantitative results from the MSI experiments were compared with quantitative results from liquid chromatography (LC)-MS/MS results from brain tissue extracts. Two different quantitative MSI techniques (standard addition and external calibration) produced quantitative results comparable to LC-MS/MS data. Tissue extracts were also analyzed by MALDI wide-isolation MS/MS, and quantitative results were nearly identical to those from LC-MS/MS. These results clearly demonstrate the necessity for an internal standard for quantitative MSI experiments.

Energy-resolved collision-induced dissociation in tandem mass spectrometry

Abstract The effects of ion kinetic energy upon the low-energy collision-induced dissociation (CID) process in triple quadrupole mass spectrometry (MS/MS) are investigated. Energy-resolved CID breakdown curves are compared to those from quasi-equilibrium theory (QET) and angle-resolved mass spectrometry. The use of breakdown curves for the differentiation of isomeric ion structures is also investigated In addition. associative collisions with reactive collision gases are studied by energy-resolved MS/MS. These techniques provide a better understanding of the low-energy collision process in MS/MS and are essential in determining standard conditions for recording MS/MS library spectra

Imaging of lipids in spinal cord using intermediate pressure matrix-assisted laser desorption-linear ion trap/Orbitrap MS.

A hybrid linear ion trap/Orbitrap mass spectrometer was used to perform tandem mass spectrometry (MS/MS) experiments and high-resolution mass analysis of lipids desorbed from nerve tissue. A dramatic improvement in mass spectral resolution and a decrease in background are observed in the spectra collected from the Orbitrap mass analyzer, which allows generation of more accurate mass spectrometric images of the distribution of lipids within nerve tissue. Employment of both mass analyzers provides a rapid and reliable means of compound identification based on MS/MS fragmentation and high-resolution mass spectrometry (HRMS) accurate mass.

Synergistic Attraction of Aedes aegypti (L.) to Binary Blends of L-Lactic Acid and Acetone, Dichloromethane, or Dimethyl Disulfide

Abstract Kairomones produced by humans provide female anthropophilic mosquitoes with vital cues used in host-seeking for a blood meal. These chemicals are emanated primarily by the skin and provide the mosquitoes a means to orient themselves to humans at a relatively close range. Chemical studies of these emanations have provided new ideas for the formulation of attractant blends. We report mosquito attraction responses for three binary blends and their separate components. The blends are comprised of L-lactic acid plus either acetone, dichloromethane, or dimethyl disulfide. At the emission rates used in our bioassays, these blends synergistically attract laboratory-reared female Aedes aegypti. Carbon dioxide is not a necessary component to yield high levels of attraction with these blends. It is postulated that at least one of these synergistic blends (L-lactic acid and acetone) produces mosquito attraction behavior similar to L-lactic acid and CO2.

Electrospray ionization tandem mass spectrometry collision‐induced dissociation study of explosives in an ion trap mass spectrometer

Electrospray ionization (ESI) tandem mass spectrometry collision-induced dissociation (CID) fragmentation processes of a series of nitroaromatic, nitramine and nitrate ester explosives were studied in the negative-ion mode using daughter-ion, parent-ion and neutral loss scans. 2,4,6-Trinitrotoluene (TNT) was characterized by loss of OH, NO and NO2. 1,3,5-Trinitro-1,3,5-triazacyclohexane (RDX) and 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX) were characterized by loss of CH2NNO2, NNO2, NO2 and N2O. 2,4,6,N-Tetranitro-N-methylaniline (tetryl) and its hydrolysis product, N-methylpicramide, showed losses of NO2, HNO2 and NNO2. Pentaerythritol tetranitrate (PETN), glycerol trinitrate (nitroglycerin) and ethylene glycol dinitrate (EGDN) were characterized by loss of CH2NO2, CH2NO, CHNO2, ONO2, NO2 and NO. Similarities were found between ESI and negative chemical ionization mass spectra as well as between their CID fragmentation processes. Detection limits of TNT, tetryl, PETN, RDX and HM were found to be in the 5–10 pg range.

Quantitative Tandem Mass Spectrometric Imaging of Endogenous Acetyl-l-carnitine from Piglet Brain Tissue Using an Internal Standard

Matrix-assisted laser desorption/ionization (MALDI) based mass spectrometric imaging (MSI) is increasingly being used as an analytical tool to evaluate the molecular makeup of tissue samples. From the direct analysis of a tissue section, the physical integrity of sample is preserved; thus, spatial information of a compounds distribution may be determined. One limitation of the technique, however, has been the inability to determine the absolute concentration from a tissue sample. Here we report the development of a quantitative MSI technique in which the distribution of acetyl-L-carnitine (AC) in a piglet brain sample is quantified with MALDI MSI. An isotopically labeled internal standard was applied uniformly beneath the tissue section, and wide-isolation tandem mass spectrometry was performed. Normalizing the analyte ion signal by the internal standard ion signal resulted in significant improvements in MS images, signal reproducibility, and calibration curve linearity. From the improved MS images, the concentration of AC was determined and plotted producing a concentration-scaled image of the distribution of AC in the piglet brain section.