Simultaneously quantifying parent drugs and screening for metabolites in plasma pharmacokinetic samples using selected reaction monitoring information-dependent acquisition on a QTrap instrument

Bioanalytical support of plasma pharmacokinetic (PK) studies for drug discovery programs primarily involves the quantitative analysis of dosed compounds using liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/MS/MS) operated in selected reaction monitoring (SRM) mode. However, there is a growing need for information on the metabolism of new chemical entities (NCEs), in addition to the time-concentration profiles from these studies. In this paper, we present a novel approach to not only quantify parent drugs with SRM, but also simultaneously screen for metabolites using a hybrid triple quadrupole/linear ion trap (QqQ(LIT)) instrument. This was achieved by incorporating both the conventional SRM-only acquisition of parent compounds and the SRM-triggered information-dependent acquisition (IDA) of potential metabolites within the same scan cycle during the same LC/MS/MS run. Two test compounds were used to demonstrate the applicability of this approach. Plasma samples from PK studies were processed by simple protein precipitation and the supernatant was diluted with water before injection. The fast scanning capability of the linear ion trap allowed for the information-dependent acquisition of metabolite MS/MS spectra (<1 s/scan), in addition to the collection of adequate data points for SRM-only channels. The MS/MS spectra obtained from potential metabolites in post-dose samples correlated well with the spectra of the parent compounds studied, therefore providing additional confirmatory structure information without the need for repetitive analyses. Relative quantitative time-concentration profiles of identified metabolites were also obtained. Furthermore, this articulated SRM+SRM-IDA approach generated equivalent quantitative results for parent compounds to those obtained by conventional SRM-only analysis. This approach has been successfully used to support discovery PK screening programs.     

Search for neutral, long-lived particles decaying into two muons in pp[over] collisions at sqrt[s]=1.96 TeV

We present a search for a neutral particle, pair produced in pp[over] collisions at sqrt[s]=1.96 TeV, which decays into two muons and lives long enough to travel at least 5 cm before decaying. The analysis uses approximately 380 pb(-1) of data recorded with the D0 detector. The background is estimated to be about one event. No candidates are observed, and limits are set on the pair-production cross section times branching fraction into dimuons + X for such particles. For a mass of 10 GeV and lifetime of 4x10(-11) s, we exclude values greater than 0.14 pb (95% C.L.). These results are used to limit the interpretation of NuTeV's excess of dimuon events.     

Electron-cyclotron-resonance plasma heating with broadband microwave radiation: Anomalous effects

Affects of microwave bandwidth on the high-charge-states of ion beams extracted from a conventional minimum-B-geometry ECR ion source are first demonstrated. The high-charge-state intensities, produced with broadband microwave radiation are observed to be factors ?2 than those produced with narrow bandwidth microwave radiation at the same power level.     

Bounds on an anomalous dijet resonance in W+jets production in pp collisions at √s = 1.96 TeV

We present a study of the dijet invariant mass spectrum in events with two jets produced in association with a W boson in data corresponding to an integrated luminosity of 4.3 fb(-1) collected with the D0 detector at √s = 1.96 TeV. We find no evidence for anomalous resonant dijet production and derive upper limits on the production cross section of an anomalous dijet resonance recently reported by the CDF Collaboration, investigating the range of dijet invariant mass from 110 to 170 GeV/c(2). The probability of the D0 data being consistent with the presence of a dijet resonance with 4 pb production cross section at 145 GeV/c(2) is 8×10(-6).     

Weak norms of random sums

Let denote a sequence of measurable functions on , and let denote the weak norm. It is shown that

where is a sequence of independent random variables taking on values and with equal probability. Moreover, it is shown that

The paper concludes by providing an example indicating that, if , then the estimate

is the best possible.

     

Hamilton-Jacobi expansion of the scattering amplitude

The calculation of the scattering amplitude is reduced to the problem of solving a set of classical Hamilton-Jacobi equations. This allows one to incorporate classical intuition into approximations at a fundamental level. The result is actually an iterative expansion for the scattering amplitude which is expected to be convergent in the high-energy limit. The first term in the expansion is shown to be the Glauber approximation, which is an approximation used extensively in nuclear as well as atomic and particle physics.     

Study of Zgamma events and limits on anomalous ZZgamma and Zgammagamma couplings in pp collisions at square root s = 1.96 TeV

We present a measurement of the Zgamma production cross section and limits on anomalous ZZgamma and Zgammagamma couplings for form-factor scales of lambda = 750 and 1000 GeV. The measurement is based on 138 (152) candidates in the eegamma (mumugamma) final state using 320(290) pb(-1) of pp(-1) collisions at square root of s = 1.96 TeV. The 95% C.L. limits on real and imaginary parts of individual anomalous couplings are /h(10,30)Z/ < 0.23, /h(20,40)Z/ < 0.020, /h(10,30)gamma/ < 0.23, and /h(20,40)gamma/ < 0.019 for lambda = 1000 GeV.     

Measurement of the Lambda0b lifetime in the decay lambda0b--> J/psiLambda0 with the D0 detector

We present measurements of the Lambda(0)(b) lifetime in the exclusive decay channel Lambda(0)(b)--> J/psiLambda(0), with J/psi--> mu(+)mu(-) and Lambda(0)--> ppi(-), the B0 lifetime in the decay B0-->J/psiK(0)(S) with J/psi--> mu(+)mu(-) and K(0)(S)-->pi(+)pi(-), and the ratio of these lifetimes. The analysis is based on approximately 250 pb(-1) of data recorded with the D0 detector in pp collisions at sqrt[s] = 1.96 TeV. The Lambda(0)(b) lifetime is determined to be tau(Lambda(0)(b)) = 1.22(+0.22)(-0.18)(stat) +/- 0.04(syst) ps, the B0 lifetime tau(B0) = 1.40(+0.11)(-0.10)(stat) +/- 0.03(syst) ps, and the ratio tau(Lambda(0)(b))/tau(B0) = 0.87(+0.17)(-0.14)(stat) +/- 0.03(syst). In contrast with previous measurements using semileptonic decays, this is the first determination of the Lambda(0)(b) lifetime based on a fully reconstructed decay channel.