Capillary electrophoresis for rapid identification of monoclonal antibodies for routine application in hospital

mAbs are widely used in cancer therapy. Their compounding, performed just before their administration to patients, is executed in a production unit of the hospital. Identification of these drugs, individually prepared in bags for infusion before patient administration, is of paramount importance to detect potential mistakes during compounding stage. A fast and reliable analytical method based on CZE combined to a cationic capillary coating (hexadimethrine bromide) was developed for identification of the most widely used compounded therapeutic for cancer therapy (bevacizumab, cetuximab, rituximab, and trastuzumab). Considering the high structural and physico‐chemical similarities of these mAbs, an extensive optimization of the BGE composition has been performed. The addition of perchlorate ions and polysorbate in the BGE greatly increased the resolution. To validate the method, an internal standard was used and the relative migration times (RTm) were estimated. Very satisfactory RSDs of the RTm for rituximab (0.76%), cetuximab (0.46%), bevacizumab (0.31%), and trastuzumab (0.60%) were obtained. The intraday and interday RSD of the method were less than 0.32 and 1.3%, respectively for RTm. Significant differences between theses RTms have been demonstrated allowing mAbs identification. Finally, accurate mAbs identification has been demonstrated by a blind test.     

Slipping zone location in squeeze flow

In squeeze flow rheometry, the main problem is the boundary condition between the squeezed material and the plates. Therefore, the crucial assumption is to know the location and the shape of the sample part where wall slip may or may not occur. This question is investigated from experimental results. For this, squeeze flow experiments are carried out to visualize the flow pattern at the walls. Influence of boundary conditions is particularly studied using different plate surface condition. As a result, with wall slipping conditions, we propose a flow modelling divided into two zones: a circular central zone of the sample sticks on the plates and, beyond that zone, the sample slips at the plates with friction.     

Mean stress in a granular medium in dynamics

In this paper we propose to construct a mean stress tensor for a granular medium, valid in static and in dynamics, which takes into account the contact reactions and the body forces acting at the grain level. A simple analytical example shows that taking account of inertia forces is essential to insure the symmetry of the mean stress tensor in dynamics. Finally, numerical simulations illustrating this definition of the mean stress tensor are presented for a granular medium ensiled.     

Understanding and improving direct UV detection of monosaccharides and disaccharides in free solution capillary electrophoresis

Direct UV detection of carbohydrates in free solution capillary electrophoresis at 270 nm is made possible by a photo-oxidation reaction. Glucose, rhamnose and xylose were shown to have unique UV absorption spectra hypothesizing different UV absorbing intermediates for their respective photo-oxidation. NMR spectroscopy of the photo-oxidation end products proved they consisted of carboxylates and not malondialdehyde as previously theorized and that oxygen thus plays a key role in the photo-oxidation pathway. Adding the photo-initiator Irgacure^® 2959 in the background electrolyte increased sensitivity by 40% at an optimum concentration of 1 × 10⁻⁴ mM and 1 × 10⁻⁸ mM for conventional 50 μm i.d. capillaries and for the corresponding extended light path capillaries, respectively.     

Local pressure components and surface tension of spherical interfaces. Thermodynamic versus mechanical definitions. I. A mesoscale modeling of droplets

We report mesoscale simulations of spherical drops to investigate the surface tension and mechanical properties. The Monte Carlo simulations are performed with the multibody potential commonly used in the many-body dissipative particle dynamics simulations. We establish here the calculation of the local normal and transverse components of the pressure tensor via the perturbation volume within the thermodynamic route. The different profiles of these components are compared to those calculated using the mechanical approach. To complete the mesoscale modeling of drops, we investigate the curvature dependence of the surface tension in order to calculate the Tolman's length, which is found to be negative.     

Thermodynamic evaluation and optimization of the Li,Na, K,Mg, Ca,Sr // F,Cl reciprocal system

A complete critical evaluation of all available phase diagram and thermodynamic data has been performed for all condensed phases of the (LiF + LiCl + NaF + NaCl + KF + KCl + MgF₂ + MgCl₂ + CaF₂ + CaCl₂ + SrF₂ + SrCl₂) system, and optimized model parameters have been found. The (LiCl + NaCl + KCl + MgCl₂ + CaCl₂ + SrCl₂), (LiF + NaF + KF + MgF₂ + CaF₂ + SrF₂), and (LiF + LiCl + NaF + NaCl + KF + KCl + MgF₂ + MgCl₂ + CaF₂ + CaCl₂) subsystems have been critically evaluated previously. The model parameters for the common-ion binary, common-anion ternary, and reciprocal ternary subsystems (i.e. systems with two cations and two anions) can be used to predict thermodynamic properties and phase equilibria for the multicomponent reciprocal system. The Modified Quasichemical Model in the Quadruplet Approximation was used for the molten salt phase. This model takes into account both first-nearest-neighbor (cation–anion) and second-nearest-neighbor (cation–cation and anion–anion) short-range ordering, and the coupling between them. Finally, the CaFCl–SrFCl solid solution was modeled using the Compound Energy Formalism.     

Thermodynamic evaluation and optimization of the (NaCl + KCl + MgCl2 + CaCl2 + ZnCl2) system

A complete critical evaluation of all available phase diagram and thermodynamic data has been performed for all condensed phases and relevant gaseous species of the (NaCl + KCl + MgCl₂ + CaCl₂ + ZnCl₂) system, and optimized model parameters have been found. The (NaCl + KCl + MgCl₂ + CaCl₂) subsystem has been critically evaluated in a previous article. The model parameters obtained for the binary and ternary subsystems can be used to predict thermodynamic properties and phase equilibria for the multicomponent system. The Modified Quasichemical Model for short-range ordering was used for the molten salt phase.     

Development and validation of a ultra-high-performance liquid chromatography-UV method for the detection and quantification of erectile dysfunction drugs and some of their analogues found in counterfeit medicines

Pharmaceutical counterfeiting is a permanently growing problem. Control laboratories are constantly analysing counterfeit medicines. In industrialised countries, one of the main counterfeited class of medicines are erectile dysfunction drugs. This paper describes the development and validation of a fast method to detect and quantify the three authorised phosphodiesterase type 5 inhibitors and five analogues. The method is based on the use of a sub-2 microns polar-embedded column with a gradient using acetonitrile as organic modifier and 10 mM ammonium formate buffer (pH 3.5) as aqueous component of the mobile phase. The separation was achieved in less than 4.5 min. The method has also been compared to the registered HPLC method for the assay of Viagra^® which was considered as the reference method. The method is also compatible with on-line coupling mass spectrometry and will significantly reduce analysis times and solvent consumption.     

Synthesis and spectral studies on some tetrahydrobenzoxanthen-11-ones: crystal and molecular structure of 9,9-dimethyl-12-(2-nitrophenyl)-8,9,10,12-tetrahydrobenzo[<Emphasis Type="Italic">a</Emphasis>]xanthen-11-one

A series of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones have been synthesized by the multicomponent reaction (MCR) of β-naphthol, aryl aldehydes, and dimedone by using BF₃:OEt₂ as a catalyst. The derived compounds have been analyzed by IR, NMR (1D and 2D), and mass spectra. The single crystal X-ray structural analysis of 9,9-dimethyl-12-(2-nitrophenyl)-8,9,10,12-tetrahydrobenzo[a]-xanthen-11-one evidences the envelope conformation of the cyclohexane ring and the pyran ring tends to adopt flattened-boat conformation.     

Optimization of extraction procedure and chromatographic separation of glyphosate, glufosinate and aminomethylphosphonic acid in soil

Analysing herbicides in soil is a complex issue that needs validation and optimization of existing methods. An extraction and analysis method was developed to assess concentrations of glyphosate, glufosinate and aminomethylphophonic acid (AMPA) in field soil samples. After testing extractions by accelerated solvent extraction and ultrasonic extraction, agitation was selected with the best recoveries. Water was preferred as solvent extraction because it resulted in a cleaner chromatogram with fewer impurities than was the case with alkaline solvents. Analysis was performed by FMOC pre-column derivatization followed by high-performance liquid chromatography (HPLC) on a 300 mm C(18) column which permitted enhanced separation and sensitivity than a 250 mm C(18) column and increased resistance than the NH(2) column for soil samples. This extraction and analysis method allowing a minimum of steps before the injection in the HPLC with fluorescence detection is efficient and sensitive for a clay-loamy soil with detection limits of 103 μg kg(-1) for glyphosate, 15 μg kg(-1) for glufosinate and 16 μg kg(-1) for AMPA in soil samples.