N-Nitrosodimethylamine Contamination in the Metformin Finished Products

A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5–9.5 ng/mL. The assay for all substances was accurate and precise. NDMA was not detected in the acquired active pharmaceutical ingredient (API); however, NDMA was detected in 64 (85.3%) and 22 (91.7%) of the finished product and prolonged finished product samples, respectively. European Medicines Agency recommends the maximum allowed limit of 0.032 ppm in the metformin products. Hence, 28 finished products and 7 pronged dosage products were found to exceed the acceptable limit of daily intake of NDMA contamination. The implications of our findings for the testing of pharmaceutical products are discussed.     

Identification of chaos in a cutting process by the 0–1 test

We have examined the cutting process by using a two degrees of freedom non-smooth model with a friction component. Instead of the standard Lyapunov exponent treatment a statistical ‘0–1’ test based on the asymptotic properties of a non-harmonic Brownian motion chain has been successively applied to reveal the nature of the cutting process. In this test we calculated the control parameter K which is approaching asymptotically to 0 or 1 for regular and chaotic motions, respectively. The presented approach is independent on the integration procedure as we defined a characteristic distance between the points forming the time series used in the test separately.     

On Conformal Infinity and Compactifications of the Minkowski Space

Using the standard Cayley transform and elementary tools it is reiterated that the conformal compactification of the Minkowski space involves not only the “cone at infinity” but also the 2-sphere that is at the base of this cone. We represent this 2-sphere by two additionally marked points on the Penrose diagram for the compactified Minkowski space. Lacks and omissions in the existing literature are described, Penrose diagrams are derived for both, simple compactification and its double covering space, which is discussed in some detail using both the U(2) approach and the exterior and Clifford algebra methods. Using the Hodge *{\star} operator twistors (i.e. vectors of the pseudo-Hermitian space H _2,2) are realized as spinors (i.e., vectors of a faithful irreducible representation of the even Clifford algebra) for the conformal group SO(4, 2)/Z ₂. Killing vector fields corresponding to the left action of U(2) on itself are explicitly calculated. Isotropic cones and corresponding projective quadrics in H _p,q are also discussed. Applications to flat conformal structures, including the normal Cartan connection and conformal development has been discussed in some detail.     

Nanoadhesion on Rigid Methyl‐Terminated Biphenyl Thiol Monolayers: A High‐Rate Dynamic Force Spectroscopy Study

Nanoadhesion on a self‐assembled monolayer of 4‐methyl‐4′‐mercaptobiphenyl is measured using a modified atomic force microscope. The dependence of the adhesion force on the loading rate is analyzed with the Dudko–Hummer–Szabo model, and the kinetic and interaction potential parameters for a single terminal group are extracted. The energy and location of the activation barrier suggest that the adhesion is dominated by van der Waals dispersion forces. The humidity effect on the nanoadhesion is also studied. The results are compared with previously measured values for methyl‐terminated alkane thiols and the influence of the thiol rigidity on the adhesion force is discussed.     

New Insights into Cinchonine–Aluminium Complexes and Their Application as Chiral Building Blocks: Unprecedented Ligand‐Exchange Processes in the Presence of ZnR2 Compounds

Previous studies have demonstrated that [(CN)₂AlCl] and [R₂Al(μ‐CN)]₂ (CN=deprotonated cinchonine) complexes can effectively act as chiral, semirigid, N,N‐ditopic metalloligands for Zn‐containing nodes, and provide viable means for constructing new, homochiral, heterometallic, coordination polymers of zigzag and helical topologies. These findings have prompted further investigations on the organometallic analogues of the formula [(CN)₂AlR], anticipating their utility as N,N‐metalloligands for ZnR₂ units. Surprisingly, reactions of [(CN)₂AlMe]‐type metalloligands with ZnR₂ compounds (R=Me or Et) revealed unprecedented ligand‐exchange processes, including zinc‐to‐aluminium and aluminium‐to‐zinc transmetalations of alkyl groups. The molecular and crystal structure of the resulting compounds was determined by X‐ray diffraction analysis. From the reaction of [(CN)₂AlMe] with ZnMe₂ a new pseudopolymorphic form of a noncovalent porous material based on [Me₂Al(μ‐CN)]₂ molecules was isolated. Strikingly, the analogous reaction involving ZnEt₂ led to the generation of a new chiral 4N‐tetratopic heterometalloligand [(CN)EtAl(μ‐CN)₂ZnEt]. The latter unit was successfully connected by alkyl‐exchanged ZnMe₂ nodes to give an original homochiral heterometallic {[(CN)EtAl(μ‐CN)₂ZnEt]ZnMe₂}_n coordination polymer adopting a snake 1D motif. The outcome of the revealed reactions indicates the complicated multistep reaction route that involves redistribution of cinchonine and alkyl ligands among the Al and Zn centers, and a general reaction scheme is proposed. The results are in strong contrast with the previously studied inorganic–organic [(CN)₂AlCl/ZnCl₂] system, which exclusively affords a helical coordination polymer based on ZnCl₂ nodes and (CN)₂AlCl metalloligands and lacks the exchange of CN ligands.     

Synthesis, structure and unique reactivity of the ethylzinc derivative of a bicyclic guanidine

An equimolar reaction between ZnEt(2) and 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine (hppH) results in the formation of EtZn(hpp) (1) which crystallizes as a trinuclear agglomerate with the guanidinate ligands spanning 4-coordinate Zn centers. Exposure of a pre-formed THF solution of 1 to undried air leads to a ZnO-incorporating derivative 1(4)·ZnO, while an analogous experiment with CH(2)Cl(2) as solvent leads to a novel tetranuclear mixed aggregate formulated as [EtOZn(hpp)](2)[ClZn(hpp)](2) (2). The composition of 2 indicates that its formation proceeds via a complex multi-step reaction route that involves not only the oxygenation of ZnEt moieties, but also the activation of CH(2)Cl(2), causing the transfer of a chloride anion to the Zn center. Compounds were characterized by (1)H NMR spectroscopy and single-crystal X-ray diffraction analysis.     

Determination of azaarenes in oils using the LC‐APCI‐MS/MS technique: New environmental toxicant in food oils

A novel method to determine of azaarenes in refined and cold‐pressed vegetable oils and animal fats is reported. The method may be used to determine eight most important acridine derivatives (benz[a]acridine, dibenz[a,i]acridine, benz[c]acridine, dibenz[a,j]acridine, 7,9‐dimethylbenz[c]acridine, dibenz[a,h]acridine, dibenz[a,c]acridine, dibenz[c,h]acridine) at a high sensitivity (LOQ in the 2–25 ng kg^?1 range), high analyte recovery rates (70.7–98.7%), sufficient linearity within the studied concentration range (r > 0.97). The method is fast, simple, and needs no expensive clean‐up procedures to successfully determine the analytes. Azaarene concentration in the studied oil samples ranged from 2 to 250 ng kg^?1. Benz[a]acridine and dibenz[a,j]acridine were the compounds found most commonly and at the highest concentrations. The observed concentrations most probably reflected levels of environmental contamination of raw materials used to produce the analyzed oil/fat samples.     

Evaluating paper degradation progress. Cross-linking between chromatographic, spectroscopic and chemical results

The study presents an overview of the chromatographic (SEC), spectroscopic (FTIR, UV/VIS), viscometric (DP) and chemical methods (titration, pH) used for the evaluation of the degradation progress of various kinds of paper under various conditions. The methods were chosen to follow different routes of paper degradation. Model paper samples represented boundary paper types from pure cellulose cotton paper, through softwood to low quality acidic, sized groundwood paper The accelerated ageing conditions were adjusted to achieve maximum effect (climatic chamber RH 59%, 90^oC) and also to mimic the environment inside books (closed vials). The results were settled on the literature data on the degradation mechanisms and compared in terms of the paper types and ageing conditions. The estimators of coupled de-polymerisation and oxidation have been proposed based on the correlation between SEC, UV/VIS and titrative coppper number determination. The overall oxidation index derived from FTIR results was shown to correlate with the summary –CHO and –COOH concentration determined by titrative methods.     

Charge Fluctuations and Ethylene‐Group‐Ordering Transition in β′′‐(BEDT‐TTF)4[(H3O)Fe(C2O4)3]⋅Y Molecular Charge‐Transfer Salts

The polarized infrared reflectance and Raman spectra of the three quasi‐two‐dimensional β′′‐(BEDT‐TTF)₄[(H₃O)Fe(C₂O₄)₃]?Y bifunctional charge‐transfer salts, where BEDT‐TTF=bis(ethylenedithio)tetrathiafulvalene and Y=C₆H₅Br, (C₆H₅CN)_0.17(C₆H₅Br)_0.83, (C₆H₅CN)_0.4(C₆H₅F)_0.6, have been measured as a function of the temperature. Signatures of charge inhomogenity have been found in both Raman and infrared spectra of the β′′‐(BEDT‐TTF)₄[(H₃O)Fe(C₂O₄)₃]?Y superconductors. A 100 K transition to a mixed insulating/metallic state is clearly seen for the first time in the temperature dependence of the electronic spectra of superconducting β′′‐(BEDT‐TTF)₄[(H₃O)Fe(C₂O₄)₃]?C₆H₅Br. We suggest that this phase transition is due to subtle changes in the ethylene groups ordering, which are related to a structural phase transition in the anionic layer. The infrared and Raman spectra of quasi‐two‐dimensional metal α‐′pseudo‐κ′‐(BEDT‐TTF)₄[(H₃O)Fe(C₂O₄)₃]C₆H₄Br₂ are also investigated.