A study of the centrally producedK *0 K^{*0} \bar K^{*0} final state in the reactionpp→p f (K + K -π+π-)p s at 300 GeV/c

The reactionpp→p _f (K ⁺ K ^-π⁺π^-)p _s , where theK ⁺ K ^? π⁺π^- system is centrally produced, has been studied at 300 GeV/c. TheK ^*0 \(K^{*0} \bar K^{*0} \) final state has been observed and the cross sections for its central production are found to be the same at 300 and 85 GeV/c. TheK ^*0 \(K^{*0} \bar K^{*0} \) final state appears to be produced as a non-resonant threshold enhancement.     

A study of common discovery dosing formulation components and their potential for causing time-dependent matrix effects in high-performance liquid chromatography tandem mass spectrometry assays

Hydroxyproyl-beta-cyclodextran (HPBCD), methyl cellulose (MC), Tween 80 and PEG400 are commonly used in dosing formulations in pharmacokinetic (PK) studies during the early drug discovery stage. A series of studies was designed to evaluate the potential matrix effects of these dosing vehicles when the samples are assayed by high-performance liquid chromatography combined with tandem mass spectrometry (HPLC/MS/MS). These dosing vehicles were dosed into the rats via either an intravenous (IV) or an oral route (PO) and plasma samples were collected for a 24-h post-dose period. Five test compounds with CLog P values ranging from 0.9 to 5.4 were spiked into the collected rat plasma. After protein precipitation, these samples were analyzed using a generic fast-gradient HPLC/MS/MS method. Three popular mass spectrometers (Thermo-Finnigan Quantum with ESI and APCI, AB-Sciex API 3000 with ESI and APCI, and Waters-Micromass Quattro Ultima with ESI) were used to test these plasma samples. Results indicated that there was no observed matrix effect for all five compounds when 20% HPBCD or 0.4% MC was used as the vehicle in either the IV or the PO route, respectively. In addition, 0.1% Tween 80 dosed either IV or PO caused significant ion suppression (50-80%, compared to results obtained from plasma samples free from vehicles) for compounds that eluted at the beginning of the chromatogram. Also, PEG400 when used in an oral formulation caused significant ion suppression (30-50%) for early eluting compounds. These matrix effects were not only ionization mode (ESI or APCI) dependent, but also source design (Thermo-Finnigan, AB-Sciex or Waters-Micromass) dependent. Overall, the APCI mode proved to be less vulnerable to matrix effects than the ESI mode. Some possible mechanisms of these matrix effects are proposed and simple strategies to avoid these matrix effects are discussed.     

Unique thermospray mass spectrometry of 1,4-benzoquinone and analogs in ammonium acetate solutions

In general, ions corresponding to [M + H]⁺ and/or [M + NH₄]⁺ are observed in thermospray mass spectrometry (TSMS) when using ammonium acetate in the liquid carrier. For several quinones investigated, unique thermospray mass spectra were detected with a mass spectral peak corresponding to an [M + 16]⁺ ion being observed in aqueous ammonium acetate solutions. Investigation of l,4-benzoquinone (BQU) and structurally analogous quinones indicated that amine conjugate formation with BQU and similar quinones was the origin of the unique [M + 16]⁺ ion in TSMS. When methanol was added to the liquid carrier, ions corresponding to methoxy conjugation were detected. High-performance liquid chromatography followed by TSMS or electrochemical detection gave evidence that this amine and methoxy conjugate formation was occurring in the thermospray source area.     

GC/MS characterization of urinary metabolites of doxylamine succinate: Identification of the aglycones formed from intestinal microflora metabolism of the polar glucuronide metabolites

This study describes the use of high performance liquid chromatography (HPLC) and capillary gas chromatography/mass spectrometry (GC/MS) in the characterization of polar glucuronide conjugates of doxylamine and their subsequent aglycones following deconjugation. Rat urinary extracts which contained doxylamine and both nonconjugated and conjugated doxylamine metabolites, were examined by HPLC before and after incubation with rat intestinal microflora. The subsequent deconjugated urinary metabolites and the nonconjugated products remaining in the urinary extracts were then isolated, acetylated, and assayed by GC/MS. Incubation with the intestinal microflora indicated that anaerobic bacteria were capable of effecting hydrolytic cleavage of these polar O-glucuronide metabolites of doxylamine and its demethylated products to their subsequent aglycones. GC/MS analysis was performed using a fused silica DB-5 GC column and was utilized for the identification of these deconjugated metabolites.     

Characterization of the mycotoxin fumonisin B1: comparison of thermospray, fast-atom bombardment and electrospray mass spectrometry.

The utility of thermospray mass spectrometry (TSMS), fast-atom bombardment mass spectrometry (FABMS), and electrospray mass spectrometry (ESMS) for the analysis of Fumonisin B1 is investigated. In addition, the analysis of two different standards of Fumonisin B1 as well as an inoculated corn culture extract that contained Fumonisin B1 is reported. The results of these efforts show that ESMS, as well as FABMS and a combination of FAB and tandem mass spectrometry (FABMS/MS), provide useful data for the characterization of Fumonisin B1. The detection limit was 50 pg for Fumonisin B1 when analyzed by full scan FABMS, and 5 pg when analyzed by single-reaction monitoring FABMS/MS.     

Measurement of the structure functionsF 2 andxF 3 and comparison with QCD predictions including kinematical and dynamical higher twist effects

The isoscalar nucleon structure functionsF ₂(x, Q ²) andxF ₃(x, Q ²) are measured in the range 0<Q ²<64 GeV², 1.7<W ²<250 GeV²,x<0.7 using ν and \(\bar v\) interactions on neon in BEBC. The data are used to evaluate possible higher twist contributions and to determine their impact on the evaluation of the QCD parameter Λ. In contrast to previous analyses reaching to such lowW ² values, it is found that a low \(\Lambda _{\overline {MS} } \) value in the neighbourhood of 100 MeV describes the data adequately and that the contribution of dynamical higher twist effects is small and negative.     

Study of theK + K − π+ π− system centrally produced in the reactions π+ p→π+(K + K − π+ π−)p andpp→p(K + K − π+ π−)p at 85 GeV/c

The reactions π⁺ p→π⁺(K ⁺ K ^? π⁺ π^? p andpp→p(K ⁺ K ^? π⁺ π^?)p where the (K ⁺ K ^? π⁺ π^?) system is centrally produced have been studied at 85 GeV/c. 48% of the final state proceeds through single or double vector meson resonant production i.e.,K ^*0(890) (37%), ? (4%),ρ ⁰ (7%). Evidence is found for associatedK ^*0 (890) \(\bar K\) ^*o (890) production (6.4±1.1%) with a cross section ten times higher than that found for associated ? ? production in the same experiment.     

A measurement of $K^{*\pm}$ production in the hyperon beam experiment at CERN

We report on a measurement of the differential cross sections of inclusive production in and neutron beams. A strong leading particle effect was observed for production by . The measured –distributions are compared with calculations based on the Lund model (PYTHIA) and the quark-gluon string model. Received: 6 August 2001 / Revised version: 3 September 2001 / Published online: 5 October 2001     

Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissue

Matrix-assisted laser desorption/ionization hyphenated with quadrupole time-of-flight (QTOF) mass spectrometry (MS) has been used to directly determine the distribution of pharmaceuticals in rat brain tissue slices which might unravel their disposition for new drug development. Clozapine, an antipsychotic drug, and norclozapine were used as model compounds to investigate fundamental parameters such as matrix and solvent effects and irradiance dependence on MALDI intensity but also to address the issues with direct tissue imaging MS technique such as (1) uniform coating by the matrix, (2) linearity of MALDI signals, and (3) redistribution of surface analytes. The tissue sections were coated with various matrices on MALDI plates by airspray deposition prior to MS detection. MALDI signals of analytes were detected by monitoring the dissociation of the individual protonated molecules to their predominant MS/MS product ions. The matrices were chosen for tissue applications based on their ability to form a homogeneous coating of dense crystals and to yield greater sensitivity. Images revealing the spatial localization in tissue sections using MALDI-QTOF following a direct infusion of (3)H-clozapine into rat brain were found to be in good correlation with those using a radioautographic approach. The density of clozapine and its major metabolites from whole brain homogenates was further confirmed using fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) procedures.     

Fast mass spectrometry-based methodologies for pharmaceutical analyses

Historically, most bioanalytical methods for drug analysis in pharmaceutical industry were developed using HPLC coupled with UV or fluorescence detection. However, there is a trend toward interfacing separation technologies with more sensitive tandem mass spectrometry (MS/MS)-based systems. MS/MS detection offers complete resolution of the parent compounds from their first pass metabolites to avoid extra efforts for separation and sample clean-up procedures resulting in shorter run times. With the increasing demand for ever faster screening, there is a continuing demand for bioanalytical methods possessing higher sample throughput for both in vitro and in vivo drug metabolism and pharmacokinetic evaluations to accelerate the discovery process. This review focuses on the current approaches for fast MS-based assays (cycle-time less than 5 min) of pharmaceuticals and their metabolites that have been reported in the peer-reviewed publications.