Sensitive,High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy

The antihyerlipidemic drug atorvastatin (ATR) is used worldwide as part of the strategy to prevent cardiovascular events. The high prevalence of patient nonadherence remains an important challenge which could be addressed efficiently by precision pharmacotherapy based on therapeutic drug monitoring (TDM). ATR is metabolized to pharmacologically active metabolites, and evidence shows that the sums of ATR acid and lactone form concentrations (ATR + ATRL), or of ATR and hydroxylated metabolites (ATR + MET) should be assayed. A method is presented for the analysis of these substances in serum. Method validation included the estimation of the quantitative relationship between the concentrations and the standard deviations (SD), which supports the optimal incorporation of TDM results into nonparametric pharmacokinetic models. The concentrations of the analytes were evaluated in human subjects receiving ATR. The method’s performance improved by taking the sums of acid and lactone concentrations into account. The concentration–SD relationship was linear, and we recommend applying Theil’s regression for estimating the assay error. All analytes could be detected by 2 h post dose in the samples of human subjects. The changes in metabolite/parent drug concentration ratios in time depended on the dose. The method is suitable for the TDM of ATR with a focus on precision pharmacotherapy.     

Air Gap Microcell for Scanning Electrochemical Microscopic Imaging of Carbon Dioxide Output. Model Calculation and Gas Phase SECM Measurements for Estimation of Carbon Dioxide Producing Activity of Microbial Sources

Most of SECM studies have been carried out in liquid or gel phases. A Severinghaus type, CO₂ detecting potentiometric tip has been fabricated and used in gas phase SECM studies. The microcell tip is made without gas permeable membrane. Faster response, needed in SECM, was achieved by substituting the membrane with an air gap. The carbon dioxide concentration profile in the gas phase over a disc‐shaped colony of yeast has been detected with the new tip. Estimation of the carbon dioxide output of the fungi colony was attempted by fitting simulated curves to measured ones obtained with one dimensional (line) scans.     

Energetics of Nucleation for the Icosahedral Al–Mn Phase in HTSD-Deposited Thin Films

The cohesive energy of the Al–Mn Mackay icosahedron (MI) was estimated for different variants of chemical order, using pair-bonding energies. This problem is related to the nucleation of i-AlMn phase in sequentially deposited thin films. The chemically ordered MI comes out as the thermodynamically most stable configuration. The role of kinetic factors during deposition is also discussed.     

Temperaturabhängigkeit der Viskosität von Flüssigkeiten

Zusammenfassung Die Temperaturabhängigkeit der Viskosität von assoziierten und nicht assoziierten Flüssigkeiten wird durch eine Formel mit 3 Parametern beschrieben.Beigefügte Tabellen ermöglichen die Beurteilung der Leistungsfähigkeit dieser Funktion und einen sachlichen Vergleich mit den derzeit bekannten Gleichungen.     

Nanocomposites of Metallic Silver with Octamolybdate Amine Complexes of Nickel(II) and Copper(II)

Theoretical and Experimental Chemistry - It was shown that interaction of photoreduced octamolybdate amine complexes of nickel(II) and copper(II) with silver(I) nitrate in aqueous solutions leads...     

“Invisible” Conformers of an Antifungal Disulfide Protein Revealed by Constrained Cold and Heat Unfolding,CEST‐NMR Experiments,and Molecular Dynamics Calculations

Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two‐ and three‐state analysis of thermal unfolding, that the population of hidden states may weight 20–40 % at 298 K in a disulfide‐rich protein. In addition, sensitive ¹⁵N‐CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR “dark matter”. Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction.     

Standardisation of a <Superscript>68</Superscript>(Ge+Ga) solution within the CCRI(II)-K2.Ge-68 key comparison

This paper presents the work performed in IFIN-HH, Radionuclide Metrology Laboratory, for the standardization of a ⁶⁸(Ge+Ga) solution, within our participation in the key-comparison codified as CCRI(II)-K2.Ge-68, organised by the CIPM-CCRI(II). Four methods were used: (i) the 4πβ(PC)-γ coincidence method, efficiency extrapolation variant, (ii) the liquid scintillation counting in the variant of triple to double coincidence ratio, (iii) the gamma-ray spectrometry and (iv) the well-type ionisation chamber measurement. The final result was calculated as “power moderate weighted mean” of all results. The results obtained in all methods are presented as relative figures.     

Metal clusters in metal/C thin film nanosystems

Structure of metal clusters and of the C₆₀ matrix in Au/C₆₀ and Cu/C₆₀ nanosystems was investigated by X-ray diffraction. Results support a charge-transfer-type interaction at the metal-C₆₀ interface, which affects the size distribution of metal clusters, favouring interstitial location of metal ions in the fullerite lattice. Received 5 February 1999 and Received in final form 7 July 1999