Displaying publications 41 - 60 of 414 in total

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  1. Fulltext Search for dark matter produced in association with a leptonically decaying Z boson in proton-proton collisions at s = 13 Te
    Sirunyan AM, CMS Collaboration, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(1):13.
    PMID: 33493254 DOI: 10.1140/epjc/s10052-020-08739-5
    A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 Te , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 fb - 1 . The search uses the decay channels Z → e e and Z → μ μ . No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.
  2. Fulltext Measurements of production cross sections of the Higgs boson in the four-lepton final state in proton-proton collisions at s = 13 TeV
    CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(6):488.
    PMID: 34727143 DOI: 10.1140/epjc/s10052-021-09200-x
    Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.
  3. Fulltext Measurements of p p → Z Z production cross sections and constraints on anomalous triple gauge couplings at s = 13 TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(3):200.
    PMID: 33750993 DOI: 10.1140/epjc/s10052-020-08817-8
    The production of Z boson pairs in proton-proton ( p p ) collisions, p p → ( Z / γ ∗ ) ( Z / γ ∗ ) → 2 ℓ 2 ℓ ' , where ℓ , ℓ ' = e or μ , is studied at a center-of-mass energy of 13 TeV with the CMS detector at the CERN LHC. The data sample corresponds to an integrated luminosity of 137 fb - 1 , collected during 2016-2018. The Z Z production cross section, σ tot ( p p → Z Z ) = 17.4 ± 0.3 (stat) ± 0.5 (syst) ± 0.4 (theo) ± 0.3 (lumi) pb , measured for events with two pairs of opposite-sign, same-flavor leptons produced in the mass region 60 < m ℓ + ℓ - < 120 GeV is consistent with standard model predictions. Differential cross sections are also measured and agree with theoretical predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous Z Z Z and Z Z γ couplings.
  4. Fulltext Measurement of the Higgs boson production rate in association with top quarks in final states with electrons, muons, and hadronically decaying tau leptons at s = 13 TeV
    Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Erö J, et al.
    Eur Phys J C Part Fields, 2021;81(4):378.
    PMID: 34727142 DOI: 10.1140/epjc/s10052-021-09014-x
    The rate for Higgs ( H ) bosons production in association with either one ( t H ) or two ( t t ¯ H ) top quarks is measured in final states containing multiple electrons, muons, or tau leptons decaying to hadrons and a neutrino, using proton-proton collisions recorded at a center-of-mass energy of 13 TeV by the CMS experiment. The analyzed data correspond to an integrated luminosity of 137 fb - 1 . The analysis is aimed at events that contain H → W W , H → τ τ , or H → Z Z decays and each of the top quark(s) decays either to lepton+jets or all-jet channels. Sensitivity to signal is maximized by including ten signatures in the analysis, depending on the lepton multiplicity. The separation among t H , t t ¯ H , and the backgrounds is enhanced through machine-learning techniques and matrix-element methods. The measured production rates for the t t ¯ H and t H signals correspond to 0.92 ± 0.19 (stat) - 0.13 + 0.17 (syst) and 5.7 ± 2.7 (stat) ± 3.0 (syst) of their respective standard model (SM) expectations. The corresponding observed (expected) significance amounts to 4.7 (5.2) standard deviations for t t ¯ H , and to 1.4 (0.3) for t H production. Assuming that the Higgs boson coupling to the tau lepton is equal in strength to its expectation in the SM, the coupling y t of the Higgs boson to the top quark divided by its SM expectation, κ t = y t / y t SM , is constrained to be within - 0.9 < κ t < - 0.7 or 0.7 < κ t < 1.1 , at 95% confidence level. This result is the most sensitive measurement of the t t ¯ H production rate to date.
  5. Fulltext Search for a heavy vector resonance decaying to a Z  boson and a Higgs boson in proton-proton collisions at s = 13 Te
    Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Erö J, et al.
    Eur Phys J C Part Fields, 2021;81(8):688.
    PMID: 34780582 DOI: 10.1140/epjc/s10052-021-09348-6
    A search is presented for a heavy vector resonance decaying into a Z boson and the standard model Higgs boson, where the Z boson is identified through its leptonic decays to electrons, muons, or neutrinos, and the Higgs boson is identified through its hadronic decays. The search is performed in a Lorentz-boosted regime and is based on data collected from 2016 to 2018 at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 . Upper limits are derived on the production of a narrow heavy resonance Z ' , and a mass below 3.5 and 3.7 Te is excluded at 95% confidence level in models where the heavy vector boson couples predominantly to fermions and to bosons, respectively. These are the most stringent limits placed on the Heavy Vector Triplet Z ' model to date. If the heavy vector boson couples exclusively to standard model bosons, upper limits on the product of the cross section and branching fraction are set between 23 and 0.3 fb for a Z ' mass between 0.8 and 4.6 Te , respectively. This is the first limit set on a heavy vector boson coupling exclusively to standard model bosons in its production and decay.
  6. Evidence for Top Quark Production in Nucleus-Nucleus Collisions
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Nov 27;125(22):222001.
    PMID: 33315428 DOI: 10.1103/PhysRevLett.125.222001
    Ultrarelativistic heavy ion collisions recreate in the laboratory the thermodynamical conditions prevailing in the early universe up to 10^{-6}  sec, thereby allowing the study of the quark-gluon plasma (QGP), a state of quantum chromodynamics (QCD) matter with deconfined partons. The top quark, the heaviest elementary particle known, is accessible in nucleus-nucleus collisions at the CERN LHC, and constitutes a novel probe of the QGP. Here, we report the first evidence for the production of top quarks in nucleus-nucleus collisions, using lead-lead collision data at a nucleon-nucleon center-of-mass energy of 5.02 TeV recorded by the CMS experiment. Two methods are used to measure the cross section for top quark pair production (σ_{tt[over ¯]}) via the selection of charged leptons (electrons or muons) and bottom quarks. One method relies on the leptonic information alone, and the second one exploits, in addition, the presence of bottom quarks. The measured cross sections, σ_{tt[over ¯]}=2.54_{-0.74}^{+0.84} and 2.03_{-0.64}^{+0.71}  μb, respectively, are compatible with expectations from scaled proton-proton data and QCD predictions.
  7. Effect of diarrhoea on Tacrolimus trough level in a post liver transplant patient
    Tan ST, Yoong BK
    Med J Malaysia, 2020 11;75(6):734-735.
    PMID: 33219186
    Tacrolimus, which bonds to an immunophilin, FK506 binding protein (FKBP) has emerged as one of the most widely used immunosuppressant post solid organ transplantation. It offers excellent patient survival rates post-transplantation and a lesser number of acute rejections as compared to cyclosporine. Tacrolimus has a narrow therapeutic window with overexposure leading to acute and chronic forms of nephrotoxicity. Remarkably few data have been published on the overexposure to tacrolimus following mild diarrhoea in post-transplant patients who received treatment with tacrolimus. We observed a post-liver transplant patient with increased trough level of tacrolimus during severe diarrhoea with no complications following a timely adjustment on the dose of tacrolimus.
  8. Observation of the B_{s}^{0}→X(3872)ϕ Decay
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):152001.
    PMID: 33095627 DOI: 10.1103/PhysRevLett.125.152001
    Using a data sample of proton-proton collisions at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 140  fb^{-1} collected by the CMS experiment in 2016-2018, the B_{s}^{0}→X(3872)ϕ decay is observed. Decays into J/ψπ^{+}π^{-} and K^{+}K^{-} are used to reconstruct, respectively, the X(3872) and ϕ. The ratio of the product of branching fractions B[B_{s}^{0}→X(3872)ϕ]B[X(3872)→J/ψπ^{+}π^{-}] to the product B[B_{s}^{0}→ψ(2S)ϕ]B[ψ(2S)→J/ψπ^{+}π^{-}] is measured to be [2.21±0.29(stat)±0.17(syst)]%. The ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{0}→X(3872)K^{0}] is found to be consistent with one, while the ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{+}→X(3872)K^{+}] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B^{0} and B_{s}^{0} meson decays compared to B^{+}. The reported observation may shed new light on the nature of the X(3872) particle.
  9. Observation of the Production of Three Massive Gauge Bosons at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):151802.
    PMID: 33095594 DOI: 10.1103/PhysRevLett.125.151802
    The first observation is reported of the combined production of three massive gauge bosons (VVV with V=W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis is based on a data sample recorded by the CMS experiment at the CERN LHC corresponding to an integrated luminosity of 137  fb^{-1}. The searches for individual WWW, WWZ, WZZ, and ZZZ production are performed in final states with three, four, five, and six leptons (electrons or muons), or with two same-sign leptons plus one or two jets. The observed (expected) significance of the combined VVV production signal is 5.7 (5.9) standard deviations and the corresponding measured cross section relative to the standard model prediction is 1.02_{-0.23}^{+0.26}. The significances of the individual WWW and WWZ production are 3.3 and 3.4 standard deviations, respectively. Measured production cross sections for the individual triboson processes are also reported.
  10. Lithological constraints on resource economies shape the mycorrhizal composition of a Bornean rain forest
    Weemstra M, Peay KG, Davies SJ, Mohamad M, Itoh A, Tan S, et al.
    New Phytol, 2020 10;228(1):253-268.
    PMID: 32436227 DOI: 10.1111/nph.16672
    Arbuscular mycorrhizal fungi (AMF) and ectomycorrhizal fungi (EMF) produce contrasting plant-soil feedbacks, but how these feedbacks are constrained by lithology is poorly understood. We investigated the hypothesis that lithological drivers of soil fertility filter plant resource economic strategies in ways that influence the relative fitness of trees with AMF or EMF symbioses in a Bornean rain forest containing species with both mycorrhizal strategies. Using forest inventory data on 1245 tree species, we found that although AMF-hosting trees had greater relative dominance on all soil types, with declining lithological soil fertility EMF-hosting trees became more dominant. Data on 13 leaf traits and wood density for a total of 150 species showed that variation was almost always associated with soil type, whereas for six leaf traits (structural properties; carbon, nitrogen, phosphorus ratios, nitrogen isotopes), variation was also associated with mycorrhizal strategy. EMF-hosting species had slower leaf economics than AMF-hosts, demonstrating the central role of mycorrhizal symbiosis in plant resource economies. At the global scale, climate has been shown to shape forest mycorrhizal composition, but here we show that in communities it depends on soil lithology, suggesting scale-dependent abiotic factors influence feedbacks underlying the relative fitness of different mycorrhizal strategies.
  11. Studies of Charm Quark Diffusion inside Jets Using Pb-Pb and pp Collisions at sqrt[s_{NN}]=5.02  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2020 Sep 04;125(10):102001.
    PMID: 32955327 DOI: 10.1103/PhysRevLett.125.102001
    The first study of charm quark diffusion with respect to the jet axis in heavy ion collisions is presented. The measurement is performed using jets with p_{T}^{jet}>60  GeV/c and D^{0} mesons with p_{T}^{D}>4  GeV/c in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=5.02  TeV, recorded by the CMS detector at the LHC. The radial distribution of D^{0} mesons with respect to the jet axis is sensitive to the production mechanisms of the meson, as well as to the energy loss and diffusion processes undergone by its parent parton inside the strongly interacting medium produced in Pb-Pb collisions. When compared to Monte Carlo event generators, the radial distribution in pp collisions is found to be well described by pythia, while the slope of the distribution predicted by sherpa is steeper than that of the data. In Pb-Pb collisions, compared to the pp results, the D^{0} meson distribution for 4
  12. A case report of severe mycoplasma pneumonia with autoimmune haemolytic anaemia
    Roshan S, Tan SW
    Med J Malaysia, 2020 09;75(5):600-602.
    PMID: 32918437
    Mycoplasma pneumonia is a common cause of respiratory disease and more so in school going children. The spectrum of the manifestations range from haematological, dermatological, neurological, musculoskeletal, renal, cardiac and also gastrointestinal. The treatment approach has varied over time. In this report we would like to share our experience in a case of M.pneumonia with autoimmune haemolytic anaemia (AIHA).
  13. Diagnostic accuracy and ability to reduce unnecessary FNAC: A comparison between four Thyroid Imaging Reporting Data System (TI-RADS) versions
    Tan L, Tan YS, Tan S
    Clin Imaging, 2020 Sep;65:133-137.
    PMID: 32470834 DOI: 10.1016/j.clinimag.2020.04.029
    BACKGROUND: Thyroid Imaging Reporting Data System (TI-RADS) is used to characterize thyroid nodules while reducing unnecessary FNAC. Over the years, several versions of TI-RADS have been developed but there is no consensus on which TI-RADS is the best system. This study aimed to compare the diagnostic accuracy and ability of ACR TI-RADS, EU TI-RADS, K TI-RADS, AI TI-RADS to eliminate unnecessary FNAC.

    METHODS: In this prospective study, thyroid nodules were characterized by using the four TI-RADS systems and US-guided FNAC was done for nodule with the highest ACR TI-RADS score. Correlation between TI-RADS and FNAC results were analyzed.

    RESULTS: Out of 244 thyroid nodules, 100 nodules with either size <1 cm (43 nodules) non-diagnostic or inconclusive FNAC results (57 nodules) were excluded. Seven nodules (4.9%) were confirmed to be malignant on FNAC. K TI-RADS showed 100% sensitivity and NPV but the lowest specificity (40.2%). EU TI-RADS had the highest specificity (83.2%) but the lowest sensitivity (57.1%) and NPV (97.4%). ACR TI-RADS had an average sensitivity (85.7%) and NPV (98.6%). The specificity of ACR TI-RADS (51.1%) was lower than EU TI-RADS but higher than K TI-RADS. AI TI-RADS showed higher specificity (61.8% vs 51.1%, p 

  14. Fulltext Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)
    Sarin SK, Choudhury A, Lau GK, Zheng MH, Ji D, Abd-Elsalam S, et al.
    Hepatol Int, 2020 Sep;14(5):690-700.
    PMID: 32623632 DOI: 10.1007/s12072-020-10072-8
    BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis.

    METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19.

    RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p 

  15. Measurements of tt[over ¯]H Production and the CP Structure of the Yukawa Interaction between the Higgs Boson and Top Quark in the Diphoton Decay Channel
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Aug 07;125(6):061801.
    PMID: 32845700 DOI: 10.1103/PhysRevLett.125.061801
    The first observation of the tt[over ¯]H process in a single Higgs boson decay channel with the full reconstruction of the final state (H→γγ) is presented, with a significance of 6.6 standard deviations (σ). The CP structure of Higgs boson couplings to fermions is measured, resulting in an exclusion of the pure CP-odd structure of the top Yukawa coupling at 3.2σ. The measurements are based on a sample of proton-proton collisions at a center-of-mass energy sqrt[s]=13  TeV collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 137  fb^{-1}. The cross section times branching fraction of the tt[over ¯]H process is measured to be σ_{tt[over ¯]H}B_{γγ}=1.56_{-0.32}^{+0.34}  fb, which is compatible with the standard model prediction of 1.13_{-0.11}^{+0.08}  fb. The fractional contribution of the CP-odd component is measured to be f_{CP}^{Htt}=0.00±0.33.
  16. Fulltext A Cost-Effective Alternative for Lateral Femoral Wall Perforation in Anterior Cruciate Ligament (ACL) Reconstruction: A Case Report
    Tan SY, Leong WH, Ong LH, Mohd-Amin MZ
    Malays Orthop J, 2020 Jul;14(2):138-140.
    PMID: 32983390 DOI: 10.5704/MOJ.2007.023
    Lateral femoral wall perforation is a rare intra-operative complication in anterior cruciate ligament (ACL) reconstruction surgery. However, it can be challenging to manage if it occurs. We share our experience on lateral femoral wall perforation managed by a large fragment washer. A 25-year-old man with right ACL injury presented with knee instability despite physiotherapy. Anterior drawer test (ADT) and Lachman test were grade 3, glide on pivot shift was positive. During ACL reconstruction, the lateral femoral wall was perforated. Due to unavailability of the rescue endobutton and budget constraint, we passed the endobutton through a washer and allowed it to sit on the washer over the lateral femoral wall. ADT and Lachman test on post-operative 6, 12 and 24 weeks were grade 1, with a negative pivot shift test. Lysholm knee score improved from 69 pre-operatively to 98 post-operatively. Conventionally, lateral femoral wall perforation can be managed by rescue endobutton, or screw and washer post technique. As this complication is rare, the rescue endobutton may not be available at all times, and the cost of the implant is also another important factor to consider. A washer can be used as an alternative technique to manage lateral femoral wall perforation in ACL reconstruction as it is not only cost-effective but also provides stable fixation with good functional outcome.
  17. Laparoscopic splenic artery ligation in a patient with immune thrombocytopenia with intracranial haemorrhage (two clips that stopped a timebomb)
    Chan YQ, Lee ZM, Tan SL
    Med J Malaysia, 2020 07;75(4):433-435.
    PMID: 32724010
    Intracranial haemorrhage (ICH) in a patient with relapse of idiopathic thrombocytopaenic purpura (ITP) can be lethal. The site of haemorrhage, compounded by low platelets in this disease, makes its management extremely challenging, especially when a neurosurgical procedure is warranted. We report a case report of an unconventional way of increasing platelet counts in ITP rapidly in an emergency setting.
  18. Measurement of the Jet Mass Distribution and Top Quark Mass in Hadronic Decays of Boosted Top Quarks in pp Collisions at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Brandstetter J, et al.
    Phys Rev Lett, 2020 May 22;124(20):202001.
    PMID: 32501048 DOI: 10.1103/PhysRevLett.124.202001
    A measurement is reported of the jet mass distribution in hadronic decays of boosted top quarks produced in pp collisions at sqrt[s]=13  TeV. The data were collected with the CMS detector at the LHC and correspond to an integrated luminosity of 35.9  fb^{-1}. The measurement is performed in the lepton+jets channel of tt[over ¯] events, where the lepton is an electron or muon. The products of the hadronic top quark decay t→bW→bqq[over ¯]^{'} are reconstructed as a single jet with transverse momentum larger than 400 GeV. The tt[over ¯] cross section as a function of the jet mass is unfolded at the particle level and used to extract a value of the top quark mass of 172.6±2.5  GeV. A novel jet reconstruction technique is used for the first time at the LHC, which improves the precision by a factor of 3 relative to an earlier measurement. This highlights the potential of measurements using boosted top quarks, where the new technique will enable future precision measurements.
  19. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method development for screening of potential tamoxifen-drug/herb interaction via in vitro cytochrome P450 inhibition assay
    Yong YF, Tan SC, Liew MWO, Yaacob NS
    J Chromatogr B Analyt Technol Biomed Life Sci, 2020 May 08;1148:122148.
    PMID: 32416571 DOI: 10.1016/j.jchromb.2020.122148
    Screening for potential drug-drug interaction (DDI) or herb-drug interaction (HDI) using in vitro cytochrome P450 inhibition (IVCI) assays requires robust analytical methods with high sensitivity and reproducibility. Utilization of liquid chromatography-mass spectrometry (LC-MS) for analyte quantification is often hampered by the presence of non-volatile IVCI sample buffer constituents that often results in ion suppression. In this study, to enable screening of drug interactions involving tamoxifen (TAM) metabolism using IVCI-LC-MS/MS, a liquid-liquid extraction (LLE) method was developed and optimized for sample clean-up. Utilization of chloroform as extraction solvent and adjustment of sample pH to 11 was found to result in satisfactory recovery (>70%) and low ion suppression (<19%). A LC-MS/MS method was subsequently developed and validated for simultaneous quantification of major TAM metabolites, such as N-desmethyltamoxifen (NDT), endoxifen (EDF) and 4-hydroxytamoxifen (HTF) to enable IVCI sample analysis. Satisfactory separation of E-/Z-isomers of endoxifen with peak resolution (Rs) of 1.9 was achieved. Accuracy and precision of the method was verified within the linear range of 0-50 ng/mL for NDT, 0-25 ng/mL for HTF and 0-25 ng/mL for EDF (E/Z isomers). Inhibitory potency (IC50, Ki and mode of inhibition) of known CYP inhibitors and Strobilanthes crispus extract was then evaluated using the validated method. In summary, the results demonstrated applicability of the developed LLE and validated LC-MS/MS method for in vitro screening of DDI and HDI involving TAM metabolism.
  20. Bioequivalence and pharmacokinetic comparison of two fixed dose combination of Metformin/ Glibenclamide formulations in healthy subjects under fed condition
    Chang CT, Ang JY, Wong JM, Tan SS, Chin SK, Lim AB, et al.
    Med J Malaysia, 2020 05;75(3):286-291.
    PMID: 32467546
    AIM: This study is conducted to compare the pharmacokinetic profiles of two fixed dose combination of metformin/glibenclamide tablets (500mg/5 mg per tablet).

    MATERIALS AND METHODS: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2- period crossover study with a washout period of 7 days. All 28 adult male subjects were required to fast for at least 10 hours prior to drug administration and they were given access to water ad libitum during this period. Thirty minutes prior to dosing, all subjects were served with a standardized high-fat and high-calorie breakfast with a total calorie of 1000 kcal which was in accordance to the EMA Guideline on the Investigation of Bioequivalence. Subsequently, subjects were administered either the test or reference preparation with 240mL of plain water in the first trial period. During the second trial period, they received the alternate preparation. Plasma levels of glibenclamide and metformin were analysed separately using two different high performance liquid chromatography methods.

    RESULTS: The 90% confidence interval (CI) for the ratio of the AUC0-t, AUC0-∞, and Cmax of the test preparation over those of the reference preparation were 0.9693-1.0739, 0.9598- 1.0561 and 0.9220 - 1.0642 respectively. Throughout the study period, no serious drug reaction was observed. However, a total of 26 adverse events (AE)/side effects were reported, including 24 that were definitely related to the study drugs, namely giddiness (n=17), while diarrheoa (n=3), headache (n=2) and excessive hunger (n=2) were less commonly reported by the subjects.

    CONCLUSION: It can be concluded that the test preparation is bioequivalent to the reference preparation.

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