Study of the centrally producedK 1 0 K ± π∓ system at 85 GeV/c

We have analyzed theK ₁ ⁰ K ^± π^? system in the reactions π⁺/pp→π⁺/p(K ₁ ⁰ K ^± π^?)p. A spin-parity analysis of theK ₁ ⁰ K ^± π^? system in the “4C” channel confirms the existence of the 1⁺⁺ E meson which decays mainly throughK ^* \(\bar K\) . The data allow the presence of a 0^?+ wave at a level of 14% of theE/ι signal. The production ofD andE mesons in the channels where theK ₁ ⁰ K ^± π^? system is produced along with a π⁰ or π⁺π^? system is suppressed.     

Direct analysis of plasma samples for drug discovery compounds using mixed-function column liquid chromatography tandem mass spectrometry

A sensitive, efficient, high throughput, direct injection bioanalytical method based on a single column and high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) was developed for pharmacokinetic analysis of early drug discovery compounds in plasma samples. After mixing with a working solution containing an internal standard each plasma sample was directly injected into a polymer-coated mixed-function column for sample cleanup, enrichment and chromatographic separation. The stationary phase incorporates hydrophilic polyoxyethylene groups and hydrophobic groups to the polymer-coated silica. This allows proteins and macromolecules to pass through the column due to restricted access to the surface of the packing while retaining the drug molecules on the bonded hydrophobic phase. The analytes retained in the column with a largely aqueous liquid mobile phase were then chemically separated by switching to a strong organic mobile phase. The column effluent was diverted from waste to the mass spectrometer for analyte detection. Within 200 plasma sample injections the response ratio (analyte vs. internal standard, %CV = 4.6) and the retention times for analyte and internal standard were found consistent and no column deterioration was observed. The recoveries of test compound in various plasma samples were greater than 90%. The total analysis time was 相似文献   

Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used to directly analyze and image pharmaceutical compounds in intact tissue. The anti-tumor drug SCH 226374 was unambiguously determined in mouse tumor tissue using MALDI-QqTOFMS (QSTAR) by monitoring the dissociation of the protonated drug at m/z 695.4 to its predominant fragment at m/z 228.1. A second drug, compound A, was detected in slices of rat brain tissue following oral administration with doses ranging from 1-25 mg/kg. Quantitation of compound A from whole brain homogenates using routine high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedures revealed that concentrations of the drug in whole brain varied from a low of 24 ng/g to a high of 1790 ng/g. The drug candidate was successfully detected by MALDI-QqTOF in samples from each dose, covering a range of approximately two orders of magnitude. In addition, good correlation was observed between the MALDI-QqTOFMS intensities at each dose with the HPLC/MS/MS results. Thus the MALDI-MS response is proportional to the amount of drug in tissue. Custom software was developed to facilitate the imaging of small molecules in tissue using the MALDI-QqTOF mass spectrometer. Images revealing the spatial localization of SCH 226374 in tumor tissue and compound A in brain tissue were acquired.     

Development of a low volume plasma sample precipitation procedure for liquid chromatography/tandem mass spectrometry assays used for drug discovery applications

The demand for high sensitivity bioanalytical methods has dramatically increased in the drug discovery stage; in addition, there has been a growing trend of reducing the sample volume that is required for these assays. A sensitive high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedure has been developed and tested to meet these needs. The assay requires only a low plasma sample volume (10 microL) and employs a protein precipitation procedure using a 1:6 plasma/acetonitrile ratio. The supernatant is injected directly into the LC/MS/MS system using the selected reaction monitoring (SRM) procedure for detection. A generic HPLC gradient based on a methanol/water mobile phase with a flow rate set to 0.8 mL/min was used. The test method showed very good linearity between 0.1-1000 ng/mL (R2 = 0.9737), precision (%RSD = 6-9), accuracy (%RE = -2) and reproducibility (%RSD = 11). A drug discovery IV/PO study was assayed using both the new low volume method and our standard volume (50 microL) method. The correlation of the two sets of data from the two methods was excellent (R2 = 0.9287). This new assay procedure has been successfully used in our laboratory for over 100 different rat or mouse discovery PK studies.     

Chemical ionization mass spectrometry of doxylamine and related compounds

The chemical ionization mass spectrometric (CIMS) analysis of doxylamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]ethanamine, and related compounds, using both ammonia and methane as reagent gases, is discussed. The two reagent gases did not produce the same major fragment ion for doxylamine. Mechanisms for the fragmentation of doxylamine under either ammonia or methane CIMS conditions are proposed. The mechanisms explain the observation of an m/z 182 fragment ion for doxylamine analyzed under methane CIMS conditions and an m/z 184 product ion detected under ammonia CIMS conditions.     

Development of a biomarker assay for 3‐indoxyl sulfate in mouse plasma and brain by liquid chromatography/tandem mass spectrometry

This paper describes the development and partial validation of a fast, sensitive and specific ultra‐performance liquid chromatography/tandem mass spectrometric method for the determination of 3‐indoxyl sulfate (3‐IS), an endogenous compound in mammals, in mouse plasma and brain samples. The analytical method involves direct dilution of samples with water and protein precipitation with acetonitrile containing an internal standard, followed by separation of 3‐IS on a MonoChrom C₁₈ column and detected by selected reaction monitoring (SRM) in negative ionization mode using turbo ion‐spray ionization. Due to high endogenous levels of 3‐IS in control mouse plasma and brain, blank guinea pig plasma and brain were used for the preparation of standard curves and quality controls (QCs). The compound of interest was well separated from interference peaks from the matrices with a total runtime of 2.7 min under a gradient condition. The method was partially validated. The linear concentration range was 0.1 to 100 µg/mL in mouse plasma and 10 to 10,000 ng/g in mouse brain. Inter‐assay mean bias and relative standard deviation (RSD) for plasma were in the range of ?4.8% to 3.1% and 2.5% to 3.2%, respectively. Intra‐assay mean bias and RSD for plasma were in the range of ?3.3% to 1.4% and 1.9% to 2.8%, respectively. Inter‐assay mean bias and RSD for brain were in the range of ?1.8% to 3.5% and 1.7% to 8.1%, respectively. Intra‐assay mean bias and RSD for brain were in the range of ?1.7% to 3.9% and 4.1% to 7.3%, respectively. The lower limit of quantitation (LLOQ) for this assay was 0.1 µg/mL for plasma and 10 ng/g for brain. The matrix effect was not observed in both guinea pig plasma and mouse plasma. Copyright © 2009 John Wiley & Sons, Ltd.     

Ultra-performance liquid chromatography/tandem mass spectrometric determination of testosterone and its metabolites in in vitro samples

This paper describes the development and partial validation of a fast, sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometric (UPLC/MS/MS) method for the determination of testosterone (T) and its four metabolites, 6beta-OH-T, 16alpha-OH-T, 16beta-OH-T and 2alpha-OH-T, in in vitro samples. The analytical method involves direct dilution of samples with acetonitrile containing an internal standard, followed by separation of testosterone and the four metabolites on an Acquity UPLCtrade mark C(18) column and detected by selected reaction monitoring (SRM) in positive ionization mode using turbo ionspray ionization. The parent compound and its metabolites investigated were well separated (Rs >1.5) with a run time of 4 min under a gradient condition. The method was partially validated. The linear concentration range was 0.01 to 5 microM for all the compounds of interest. Inter-assay mean bias and relative standard deviation (RSD) were in the range of -12% to 8% and 4.1% to 8.5%, respectively. Intra-assay mean bias and RSD were in the range of -8.0% to 5.2% and 3.4% to 9.6%, respectively. The lower limit of quantitation for this assay was 0.01 microM. The differences in LC/MS performance were investigated by conducting a comparison of UPLC with another method previously optimized for HPLC-based separation and quantification of testosterone and its metabolites.     

Neutral transverse momentum spectra in 60 and 200A·GeV16O+nucleus and proton+nucleus reactions

Transverse momentum (p _T) distributions fo inclusive photons and neutral pions at midrapidity are measured with a lead glass calorimeter in 60 and are measured with a lead glass calorimeter in 60 and 200A·Gev¹⁶O+nucleus and and proton+nucleus reactions. Inclusive photon distributions are compared for central and peripheral reactions. The degree of centrality is determined either from the charged particle multiplicity or from the remaining projectile energy in the forward direction. Deviations from a nucleus+nucleus interaction model based upon linear extrapolation from p+p reactions are observed in central¹⁶O+Au data. The variation of theaverage transverse momentum is investigated as function of centrality. The target-mass and energy dependence of π⁰ p _T distributions are presented. For¹⁶O+Au a change of slope in these distributions is observed atp _t ≈0.8 GeV/c compatible with hydrodynamic expansion models.