A study of the centrally produced π+π−π0 system formed in the reactionpp→p f (π+π−π0)p s at 300 GeV/c

The reactionpp→p _f (π⁺π^?π⁰)p _s , where the π⁺π^?π⁰ system is centrally produced, has been studied at 300 GeV/c. The π⁺π^?π⁰ mass spectrum shows evidence for the η, ω anda ₂ (1320) as well as an enhancement in thea ₁ (1260) region. A Dalitz plot analysis of the π⁺π^?π⁰ system has been performed. Thea ₁ (1260) parameters coming from the fit of the 1⁺ S wave arem=1208±15 MeV and Γ=430±50 MeV. No evidence is found for theh ₁(1170) orh ₁(1380).     

The production ofJ/ψ in 200 GeV/A oxygen-uranium interactions

The dimuon production in 200 GeV/nucleon oxygen-uranium interactions is studied by the NA 38 Collaboration. The production ofJ/ψ, correlated with the transverse energyET, is investigated and compared to the continuum, as a function of the dimuon massM and transverse momentumPT. A value of 0.64±0.06 is found for the ratio (ψ/Continuum at highET)/(ψ/Continuum at lowET), from which theJ/ψ relative suppression can be extracted. This suppression is enhanced at lowPT.     

Production ofρ +, −, 0 (770),η(550), ω(783) andf 2(1270) mesons in\bar v neon and ν neon charged current interactions

The production of the meson resonances ?(770) (all three charge states), η(550), ω(783) andf ₂(1270) in \(\bar v\) Ne and ν Ne charged current interactions is investigated in a bubble chamber experiment with BEBC at CERN. Except for thef ₂, the main features of resonance production are reasonably well described by the Lund model, although the average resonance multiplicities are overestimated by the model by (67±30)%. The average multiplicities of all resonances, including thef ₂, are well reproduced by a semiempirical model, whose parameters were determined from hadron interaction data.     

Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery

This report addresses the continuing need for increased throughput in the evaluation of new chemical entities (NCEs) in terms of their pharmacokinetic (PK) parameters by describing an alternative procedure for increasing the throughput of the in vivo screening of NCEs in the oral rat PK model. The new approach is called "cassette-accelerated rapid rat screen" (CARRS). In this assay, NCEs are dosed individually (n = 2 rats/compound) in batches of six compounds per set. The assay makes use of a semi-automated protein precipitation procedure for sample preparation in a 96-well plate format. The liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/API-MS/MS) assay is also streamlined by analyzing the samples as "cassettes of six". Using this new approach, a threefold increase in throughput was achieved over the previously reported "rapid rat screen".     

Utility of solution electrochemistry mass spectrometry for investigating the formation and detection of biologically important conjugates of acetaminophen

On-line formation and detection of glutathione and cysteine conjugates of acetaminophen were accomplished by the interfacing of a coulometric electrochemical cell with a thermospray mass spectrometer in a flow-injection experiment using a liquid chromatographic pump. Formation of the conjugates occurred only after acetaminophen was oxidized electrochemically by a two-electron transfer to N-acetyl-p-benzoquinoneimine and reacted in a mixing tee with either glutathione or cysteine. The newly formed conjugate was detected by thermospray mass spectrometry by observing the [M + H]+ ion for the acetaminophen-glutathione conjugate at m/z 457, or the [M + H]+ ion for the acetaminophen cysteine conjugate at m/z 271. Both the glutathione and cysteine conjugates produced a common fragment ion at m/z 184. The on-line reaction of glutathione and electrochemically generated N-acetyl-p-benzoquinoneimine was monitored at varying pH. At pH 8.5 the ion intensity for the acetaminophen-glutathione conjugate was greater than at lower pH, indicating that lower proton concentration enhanced the reaction of glutathione with N-acetyl-p-benzoquinoneimine. This on-line electrochemical-thermospray mass spectrometric method demonstrated that acetaminophen conjugates may be formed and detected in the time frame of 1 s.     

Simultaneous determination of a drug candidate and its metabolite in rat plasma samples using ultrafast monolithic column high-performance liquid chromatography/tandem mass spectrometry

An ultrafast bioanalytical method using monolithic column high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) was evaluated for the simultaneous determination of a drug discovery compound and its metabolite in plasma. Baseline separation of the two compounds was achieved with run times of 24 or 30 s under isocratic or gradient conditions, respectively. The monolithic column HPLC/MS/MS system offers shorter chromatographic run times by increasing flow rate without sacrificing separation power for the drug candidate and its biotransformation product (metabolite). In this work, the necessity for adequate chromatographic resolution was demonstrated because the quantitative determination of the drug-related metabolism product was otherwise hampered by interference from the dosed drug compound. The chromatographic performance of a monolithic silica rod column as a function of HPLC flow rates was investigated with a mixture of the drug component and its synthetic metabolite. The assay reliability of the monolithic column HPLC/MS/MS system was checked for matrix ionization suppression using the post-column infusion technique. The proposed methods were successfully applied to the analysis of study rat plasma samples for the simultaneous quantitation of both the dosed drug and its metabolite. The analytical results obtained by the proposed monolithic column methods and the 'standard' silica particle-packed HPLC column method were in good agreement, within 10% error.     

It is time for a paradigm shift in drug discovery bioanalysis: from SRM to HRMS

It can be argued that the last true paradigm shift in the bioanalytical (BA) arena was the shift from high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection to HPLC with tandem mass spectrometry (MS/MS) detection after the commercialization of the triple quadrupole mass spectrometer in the 1990s. HPLC-MS/MS analysis based on selected reaction monitoring (SRM) has become the gold standard for BA assays and is used by all the major pharmaceutical companies for the quantitative analysis of new drug entities (NCEs) as part of the new drug discovery and development process. While LC-MS/MS continues to be the best tool for drug discovery bioanalysis, a new paradigm involving high-resolution mass spectrometry (HRMS) and ultrahigh-pressure liquid chromatography (uHPLC) is starting to make inroads into the pharmaceutical industry. The ability to collect full scan spectra, with excellent mass accuracy, mass resolution, 10-250 ms scan speeds and no NCE-related MS parameter optimization, makes the uHPLC-HRMS techniques suitable for quantitative analysis of NCEs while preserving maximum qualitative information about other drug-related and endogenous components such as metabolites, degradants, biomarkers and formulation materials. In this perspective article, we provide some insight into the evolution of the hybrid quadrupole-time-of-flight (Qq-TOF) mass spectrometer and propose some of the desirable specifications that such HRMS systems should have to be integrated into the drug discovery bioanalytical workflow for performing integrated qualitative and quantitative bioanalysis of drugs and related components.     

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

Background  

Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.