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IntroductionNefopam has been reported to be effective in postoperative pain control with an opioid-sparing effect, but the use of nefopam can lead to nausea and vomiting. To prevent these side effects, droperidol can be mixed with nefopam. In intensive care units, high concentrations of nefopam and droperidol in syringes can be used with a continuous flow.ObjectivesThe first objective of this work was to study the physicochemical stability of a nefopam solution 2.5 mg/mL diluted in NaCl 0.9% in polypropylene syringes immediately after preparation and after 6, 24 and 48 hours at room temperature. The second objective was to study the physicochemical stability of mixtures of nefopam 2.5 mg/mL and droperidol 52 µg/mL diluted in NaCl 0.9% in polypropylene syringes at room temperature over 48 hours.Materials and methodsThree syringes for each condition were prepared. For each time of analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography coupled to photodiode array detection. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry). pH values were measured at each time of analysis.ResultsSolutions of nefopam at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL, diluted in NaCl 0.9%, without protection from light, retained more than 90% of the initial concentration after 48 hours storage at 20–25°C. No modification in visual or subvisual evaluation and pH values were observed.ConclusionNefopam solutions at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL diluted in NaCl 0.9% were stable over a period of 48 hours at room temperature. These stability data provide additional knowledge to assist intensive care services in daily practice.

An overview on the design of nitric oxide (NO) delivering surfaces for biomedical purposes is provided, with a focus on the advances of the past 5 years. A localized supply of NO is of a particular interest due to the pleiotropic biological effects of this diatomic compound. Depending on the generated NO flux, the surface can mimic a physiological release profile to provide an activity on the vascular endothelium or an antibacterial activity. Three requirements are considered to describe the various strategies leading to a surface delivering NO. Firstly, the coating must be selected in accordance with the properties of the substrate (nature, shape, dimensions…). Secondly, the releasing and/or generating kinetics of NO should match the targeted biological application. Currently, the most promising structures are developed to provide an adaptable NO supply driven by pathophysiological needs. Finally, the biocompatibility and the stability of the surface must also be considered regarding the expected residence time of the device. A critical point of view is proposed to help readers in the design of the NO delivering surface according to its expected requirement and therapeutic purpose. This review summarizes the strategies described over the past 5 years, to design nitric oxide (NO) delivering surfaces for cardiovascular or antibacterial purposes, with an emphasis on three parameters: properties of the substrate, releasing and/or generating kinetics of NO, and biocompatibility and stability of the surface. The characteristics, advantages, limitations, and applications regarding the chosen strategies are depicted.

S-nitrosoglutathione (GSNO) is one of low molecular weight S-nitrosothiols occuring in humans. Nowadays, it is widely used as a nitric oxide donor for in vitro, ex vivo and in vivo experiments related to the investigation of its pathophysiological role as well as in clinical trials, aimed at its potential therapeutic use. Despite numerous reports on this physiological molecule, its quality control does not match the criteria required by competent pharmaceutical authorities. Hereby, an extensive physicochemical characterisation of synthesised and purified GSNO is provided for the first time. Indeed, structural identification including spectrometric, thermal and elemental analyses was consistent with the GSNO structure. An ion-pairing reversed phase HPLC system was developed to assess (i) GSNO content with UV detection at 334 nm, and (ii) fingerprint of its impurities coming from synthesis process and/or storage conditions, at 220 nm. The assynthesised product showed a content of 102.5 , with respect to a commercially available standard. The identified impurities, i.e. chloride, nitrite, nitrate, reduced glutathione and glutathione disulfide, were also quantified basing on pharmaceutical requirements. Main products released during various storage conditions (pH, temperature, dioxygen, …) were disulfide glutathione and nitrite ion. Recommendations are given for the safe use of GSNO in biological and pharmacological experiments.

Water-soluble, thiol protected cadmium telluride CdTe quantum dots (QDs) exhibit size dependent excitation/emission wavelength tunability. The heating period ensuring the growth of CdTe nanocrystals capped with thioglycolic acid (CdTeTGA) in aqueous solution is critical to reach a required/desirable diameter. Thus, reaction medium was monitored using a capillary zone electrophoresis (CZE) technique in order to select an appropriate heating time. QDs migrate as anionic species in a borate buffer pH 8.5 used as background electrolyte and they were separated according to their size (larger ones have shorter migration times), as confirmed by measuring their maximum wavelength of absorption, with on-line diode array detection. A relationship between electrophoretic mobilities and max was tentatively proposed. Efficiency of the purification process of crude QDs using multiple step alcohol precipitation was also confirmed with the developed CZE technique.

The retention behavior of natural α-, β-, and γ-cyclodextrins on a porous graphitic carbon (PGC) stationary phase is investigated. Unusual retention properties for reversed-phase chromatographic conditions are observed with acetonitrile—methanol and water—methanol mixtures as mobile phases. It is assumed that the retention process is governed not only by the standard solvophobic effect but also by specific interactions described as “CD-PGC” effect. The retention factor versus the volumetric methanol fraction in the mobile phase show second-order curves expressing this double mechanism hypothesis, van‘t Hoff plots demonstrate the contribution of these two retention processes. The retention factor of each natural cyclodextrin is shown to depend on the mobile phase property to act as a proton acceptor, according to the solvent selectivity classification described by Snyder. The “CD-PGC” effect is interpreted as an equilibrium between different interactions: cyclodextrin—PGC stationary phase, London dispersion forces, and cyclodextrin-mobile phase hydrogen bonding. The balance of these interactions may monitor the orientation of the cyclodextrin molecule facing the carbon surface, which is therefore suspected to be the major parameter of this retention mechanism.

Field-flow fractionation (FFF) is an analytical technique particularly suitable for the separation, isolation, and characterization of macromolecules and micrometer- or submicrometer-sized particles. This chromatographic-like methodology can modulate the retention of micron-sized species according to an elution mode described to date as “steric hyperlayer”. In such a model, differences in sample species size, density, or other physical parameters make particle selective elution possible depending on the configuration and the operating conditions of the FFF system. Elution characteristics of micron-sized particles of biological origin, such as cells, can be modified using media and carrier phases of different osmolarities. In these media, a cells average size, density, and shape are modified. Therefore, systematic studies of a single reference cell population, red blood cells (RBCs), are performed with 2 sedimentation FFF systems using either gravity (GrFFF) or a centrifugational field (SdFFF). However, in all cases, normal erythrocyte in isotonic suspension elutes as a single peak when fractionated in these systems. With carrier phases of different osmolarities, FFF elution characteristics of RBCs are modified. Retention modifications are qualitatively consistent with the “steric-hyperlayer” model. Such systematic studies confirm the key role of size, density, and shape in the elution mode of RBCs in sedimentation FFF for living, micron-sized biological species. Using polymers as an analogy, the RBC population is described as highly “polydisperse”. However, this definition must be reconsidered depending on the parameters under concern, leading to a matricial concept: multipolydispersity. It is observed that multipolydispersity modifications of a given RBC population are qualitatively correlated to the eluted sample band width.