Challenging Near InfraRed Spectroscopy discriminating ability for counterfeit pharmaceuticals detection

This study was initiated by the laboratories and control department of the French Health Products Safety Agency (AFSSAPS) as part of the fight against the public health problem of rising counterfeit and imitation medicines. To test the discriminating ability of Near InfraRed Spectroscopy (NIRS), worse cases scenarios were first considered for the discrimination of various pharmaceutical final products containing the same Active Pharmaceutical Ingredient (API) with different excipients, such as generics of proprietary medicinal products (PMP). Two generic databases were explored: low active strength hard capsules of Fluoxetine and high strength tablets of Ciprofloxacin. Then 4 other cases involving suspicious samples, counterfeits and imitations products were treated. In all these cases, spectral differences between samples were studied, giving access to API or excipient contents information, and eventually allowing manufacturing site identification.A chemometric background is developed to explain the optimisation methodology, consisting in the choices of appropriate pretreatments, algorithms for data exploratory analyses (unsupervised Principal Component Analysis), and data classification (supervised cluster analysis, and Soft Independent Modelling of Class Analogy). Results demonstrate the high performance of NIRS, highlighting slight differences in formulations, such as 2.5% (w/w) in API strength, 1.0% (w/w) in excipient and even coating variations (<1%, w/w) with identical contents, approaching the theoretical limits of NIRS sensitivity. All the different generic formulations were correctly discriminated and foreign PMP, constituted of formulations slightly different from the calibration ones, were also all discriminated. This publication addresses the ability of NIRS to detect counterfeits and imitations and presents the NIRS as an ideal tool to master the global threat of counterfeit drugs.     

Synthesis, structure and reactivity of palladium(II) complexes of chiral N-heterocyclic carbene-imine and -amine hybrid ligands

The synthesis and structures of chiral N-heterocyclic carbene (NHC)-N-donor complexes of silver(I) and palladium(II) are reported. The X-ray structure of an NHC-imine silver(I) complex [((nPr)CN(CHPh))AgBr](2) exhibits an Ag(2)Br(2) dimer motif where the imine group is not coordinated to the silver atom. Reaction between 2 and [PdCl(2)(MeCN)(2)] gives the palladium(II) complex [(kappa(2)-(nPr)CN(CHPh))PdCl(2)](3) that contains a chelating NHC-imine ligand as shown by single-crystal X-ray diffraction. Slow hydrolysis of related complexes [(kappa(2)-(nPr)CN(CHPh))PdCl(2)](3) and [(kappa(2)-((Ph)(2)CH)CN(CHPh))PdCl(2)](4) using triethylammonium chloride and water lead to the precipitation of single crystals of insoluble NHC-amino palladium(II) complexes [(kappa(2)-(nPr)CN(H(2)))PdCl(2)](6) and [(kappa(2)-((Ph)(2)CH)CN(H(2)))PdCl(2)](7), respectively. In the solid state, complexes 6 and 7 both exhibit intermolecular hydrogen bonding between chlorine and an amino-hydrogen atom resulting in an infinite chain structure. Substitution of an amino hydrogen for an ethyl group gives the soluble complex [(kappa(2)-(iPr)CN((H)Et))PdCl(2)](12). Reaction between two equivalents of 2 and [PdCl(2)(MeCN)(2)] gives the di-NHC complex [(kappa(1)-(nPr)CN(CHPh))(2)PdCl(2)](5) that does not contain a coordinated imine as shown by single crystal X-ray diffraction. Conproportionation between 5 and an equivalent of [PdCl(2)(MeCN)(2)] to does not occur at temperatures up to 100 degrees C in CD(3)CN.     

A Ru(terpy)(phen)-incorporating ring and its light-induced geometrical changes

A Ru(terpy)(phen) motif has been inscribed in a 39-membered ring by functionalizing the ligands and subsequently performing a cyclization reaction on the complex; by visible light irradiation, a dramatic geometrical changeover of the cyclic complex takes place which can be reversed thermally.     

Jamin Fabry-Perot interferometer

A novel type of interferometer was designed and tested experimentally. It combines the advantages of the spatial path separation used in the two-wave polarized Jamin interferometer and the high sensitivity that characterizes the multiwave Fabry-Perot interferometer. Furthermore, when it is sandwiched between crossed polarizers it shows a sensitivity to intracavity anisotropies that is proportional to the square of the Fabry-Perot interferometer's finesse.     

Bortrifluorid-katalysierte,ohne Schwermetallzusätze verlaufende Hydratisierung von Alkinen

Acetylenes are hydrated in benzene-acetonitrile mixtures in the presence of phosphoric acid saturated with boron trifluoride and in the absence of heavy metal ions to the corresponding ketones in high yields.     

Study of the hydrogen solid solution in thulium

Solid solutions of hydrogen in thulium are investigated, mainly by X-ray determinations in the temperature range 20–500°C. Several observations lead us to distinguish between two variaties α and α¹. In the range of existence of the α¹ phase, below the transition temperature of 120°C, the hydrogen interstitials induce in the metal lattice a behaviour different from that of the α phase, as concerns the phase equilibrium, the additional resistivity, and the lattice anisotropy.Several simple models are proposed for the explanation of this anomaly, encountered also in other heavy rate earth-hydrogen systems.     

A limiting absorption principle for scattering problems with unbounded obstacles

A generalized mode matching method that applies to a wide class of scattering problems is developed in the time harmonic two‐dimensional Helmholtz case. This method leads by variational means to an integro‐differential formulation whose unknown is the trace of the field on an unbounded one‐dimensional interface. The well‐posedness is proved after a careful study of the rather original functional framework. Owing to a fundamental density result—based upon some properties of a singular integral operator similar to the Hilbert transform—the limiting absorption principle related to this original formulation is established. Finally, two other situations are emphasized. Copyright © 2001 John Wiley & Sons, Ltd.