Simultaneous Determination of Levomepromazine Hydrochloride and Its Sulfoxide by UV‐Derivative Spectrophotometry and Bivariate Calibration Method

Abstract

Two spectrophotometric methods are proposed for the simultaneous quantification of levomepromazine hydrochloride (LV) and its main degradation product levomepromazine sulfoxide (LV‐SO). One of them is based on the first order derivative spectra generated by the Savitzky‐Golay algorithm (third‐order polynomial degree, Δλ=10 nm). Determination of levomepromazine hydrochloride and its sulfoxide was realized by measurements of amplitudes of derivative spectra at 332 nm and 278 nm, respectively. The Beer law was obeyed in the concentration range 1.5–50 µg/mL for LV and 2.5–50 µg/mL for LV‐SO. The second of the proposed methods utilized the bivariate calibration algorithm. The determination was performed at 302 nm for levomepromazine and at 334 nm for sulfoxide. The elaborated methods allowed determination of LV in the concentration range 1.0–25 µg/mL while LV‐SO was determined in the concentration range 2.0–50 µg/mL.     

An application of UV-derivative spectrophotometry and bivariate calibration algorithm for study of photostability of levomepromazine hydrochloride

Derivative spectrophotometry and bivariate calibration algorithm were used for study of run of photooxidation of levomepromazine hydrochloride (LV). The actual concentrations of LV and its main degradation product levomepromazine sulphoxide (LV-SO) were calculated using data provided by applied methods. The direct reading of absorbance values at 302 nm and 334 nm were employed for quantification of LV and LV-SO, respectively, in the case of bivariate method. The derivative spectrophotometric method is based on transformation of zero-order spectra into first derivative. The values of first derivative at 334 nm were used for quantification of LV while at 278 nm for assay of LV-SO. The obtained quantitative data were applied for investigation of kinetics of photodegradation of LV.     

High-performance liquid chromatography of levomepromazine (methotrimeprazine) and its main metabolites

The phenothiazine drug levomepromazine (methotrimeprazine) has five metabolites which previously have been identified in plasma from psychiatric patients. These are formed by sulphoxidation, N-demethylation, O-demethylation and aromatic hydroxylation in two different positions. A high-performance liquid chromatographic system is described for the analysis of levomepromazine and its main metabolites on a Supelcosil C18-DB column, based on ion-pair formation with sodium docecyl sulphate. The effects of variations in pH, buffer concentration, counter-ion concentration, temperature and concentration and composition of the organic solvent were examined. The six components may be analysed in 27.4 min at room temperature using 25 mM sodium dodecyl sulphate in 500 mM ammonium acetate buffer (pH 5.0)-5% v/v tetrahydrofuran in acetonitrile (50:50, v/v) as the mobile phase.     

Preparation of supported mesoporous thin films concerning template removal by supercritical fluid extraction

Thin films of silicate MCM-41 and silicate MCM-48 have been prepared on porous ceramic supports by the hydrothermal method. A comparative study of template removal has been made on supported thin films and on powder. By supercritical fluid extraction (SFE) with CH(3)OH-modified CO(2), at least 78% of the template can be removed from as-synthesized materials at 85 degrees C. X-ray diffraction (XRD) observations indicate that the resulting supported thin films after SFE are structurally stable and ordered with a weak pore contraction. The advantages of SFE over calcination in template removal are presented with a series of results obtained on supported thin films and on powder by XRD and N(2) adsorption-desorption.     

Structure of spin-coated lipid films and domain formation in supported membranes formed by hydration

An atomic force and fluorescence microscopy investigation of the structure of spin-coated lipid films is presented. In the surface of the dry film, lipids are found to orient in a conformation where acyl chains are pointing outward while laterally the individual layers of the multilamellar film exhibit a dewetting pattern similar to what is found in polymer thin films. Hydration of the film in liquid water promotes detachment of bilayers from the surface while a single membrane remains on the mica substrate. This supported membrane is highly uniform and defect-free as compared to supported membranes prepared by conventional methods. It is further demonstrated that supported membranes of binary lipid mixtures prepared by this method exhibit gel-fluid domain coexistence in accordance with expectations from the phase diagrams.     

Tuning the Reactivity of Ultrathin Oxides: NO Adsorption on Monolayer FeO(111)

Ultrathin metal oxides exhibit unique chemical properties and show promise for applications in heterogeneous catalysis. Monolayer FeO films supported on metal surfaces show large differences in reactivity depending on the metal substrate, potentially enabling tuning of the catalytic properties of these materials. Nitric oxide (NO) adsorption is facile on silver‐supported FeO, whereas a similar film grown on platinum is inert to NO under similar conditions. Ab initio calculations link this substrate‐dependent behavior to steric hindrance caused by substrate‐induced rumpling of the FeO surface, which is stronger for the platinum‐supported film. Calculations show that the size of the activation barrier to adsorption caused by the rumpling is dictated by the strength of the metal–oxide interaction, offering a straightforward method for tailoring the adsorption properties of ultrathin films.     

Bulk and surface oxygen vacancy formation and diffusion in single crystals, ultrathin films, and metal grown oxide structures

The neutral oxygen vacancy (OV) energy formation for bulk, subsurface sites at different depths from the surface and various surface sites has been estimated for single crystals, unsupported ultrathin films of MgO, CaO, and BaO, and MgO ultrathin films supported on Ag(001). From the calculated energy barriers for diffusion through the surface and from the surface to the bulk it is found that diffusion is a hindered event, especially for MgO. Nevertheless, diffusion from the terrace to step edges is largely favored while diffusion through terrace sites is less likely and surface to bulk has a very low probability. It is argued that this explains recent scanning tunneling microscopy images for MgO thin films supported on Ag(001) showing OV populating preferentially the step edge sites.     

Effect of the composition of Nafion deposition solutions on the ion-exchange properties of the Nafion films by quartz crystal microbalance sensor (QCM)

A quartz crystal microbalance (QCM) sensor system was employed to investigate the properties of Nafion films on a gold surface supported on a quartz-crystal as a function of the water content in the deposition solutions (0.5% Nafion in mixed ethanol/water). The rates of loading and unloading of the complex ion Ru(bpy)(3)(2+) through Nafion films were measured. A linear dependence of the frequency changes on the percentage of water in the deposition solution was observed for both loading and unloading. The ion-exchange distribution coefficients for Nafion films from various deposition solutions were calculated. We concluded that films cast from solutions of higher water content had more ;open' structures which allowed faster diffusion of ions. This conclusion was further supported by the results of SEM experiments.     

Vanadium oxides on aluminum oxide supports. 1. Surface termination and reducibility of vanadia films on alpha-Al2O3(0001)

Using density functional theory and statistical thermodynamics, we obtained the phase diagram of thin VnOm films of varying thickness (approximately 2-6 A, 1-6 vanadium layers) supported on alpha-Al2O3(0001). Depending on the temperature, oxygen pressure, and vanadium concentration, films with different thickness and termination may form. In ultrahigh vacuum (UHV), at room temperature and for low vanadium concentrations, an ultrathin (1 x 1) O=V-terminated film is most stable. As more vanadium is supplied, the thickest possible films form. Their structures and terminations correspond to previous findings for the (0001) surface of bulk V2O3 [Kresse et al., Surf. Sci. 2004, 555, 118]. The presence of surface vanadyl (O=V) groups is a prevalent feature. They are stable up to at least 800 K in UHV. Vanadyl oxygen atoms induce a V(2p) core-level shift of about 2 eV on the surface V atoms. The reducibility of the supported films is characterized by the energy of oxygen defect formation. For the stable structures, the results vary between 4.11 and 3.59 eV per 1/2O2. In contrast, oxygen removal from the V2O5(001) surface is much easier (1.93 eV). This provides a possible explanation for the lower catalytic activity of vanadium oxides supported on alumina compared to that of crystalline vanadia particles.     

Photooxidation Mechanism of Levomepromazine in Different Solvents

Unwanted photoinduced responses are well‐known adverse effects of most promazine drugs, including levomepromazine (LPZ, Levoprome^® or Nozinan^®). This drug is indicated in psychiatry primarily for the treatment of schizophrenia and other schizoaffective disorders. Levomepromazine's particular sedative properties make it especially fit for use in psychiatric intensive care. Nevertheless, it is photolabile under UV‐A and UV‐B light in aerobic conditions resulting in the formation of its sulfoxide. The LPZ photochemistry in acetonitrile (MeCN) is completely different from that in methanol (MeOH) and phosphate buffer solutions (PBS, pH = 7.4). The major photoproduct in PBS and MeOH under aerobic conditions is levomepromazine sulfoxide (LPZSO), although the amount is considerably higher in the aqueous environment. The corresponding main photoproduct in MeCN could not be characterized. The destruction quantum yields of LPZ in PBS, MeOH and MeCN are 0.13, 0.02 and <10^?3, respectively. It is further demonstrated that LPZSO does not form by the reaction of singlet oxygen with ground‐state LPZ. This oxidation product is actually produced by the reaction of the cation radical of LPZ (LPZ·⁺) with molecular oxygen. This cation radical in turn, is produced by an electron transfer process between the ³LPZ* and ground‐state molecular oxygen.     

Oberflächenzusammensetzung und katalytische Aktivität von Nickel–Kupfer-Legierungen

The decomposition of formic- acid vapour has been studied on annealed nickel-copper alloy films. The activity pattern of short-time annealed alloys reveals two maxima and in the range of 50% Ni a minimum. The maxima disappear, when the films are annealed for a longer time. One gets nearly the same variations of the curves of short-and long-time annealed films, when plotting the initial change of electric resistance of the films during reaction against the composition. It is concluded that depending on annealing conditions the surface of the alloys is more or less covered by a copper-rich alloy phase. This is supported by X-ray analysis, confirming the formation of two alloy phases.     

Determination of selected phenothiazines in human plasma by solid-phase extraction and liquid chromatography with coulometric detection

A new analytical method, based on liquid chromatography with coulometric detection, has been developed and applied to the determination of selected phenothiazines (chlorpromazine, promazine, fluphenazine and levomepromazine) in human plasma. The drugs were separated on a Discovery pentafluorophenylpropyl column, using a mobile phase composed of acetonitrile (32%) and a pH 1.9 phosphate buffer (68%). Promethazine was used as the internal standard. Detection was carried out at an oxidation potential of +0.500 V. A novel clean-up procedure was developed by means of solid-phase extraction, using cyanopropyl cartridges, which gave good extraction yield for all the analytes, with absolute recovery values higher than 91.0%. The detector response was linear over a plasma concentration range of 0.5-250.0 ng mL⁻¹ for chlorpromazine, promazine and levomepromazine and of 0.2-4.0 ng mL⁻¹ for fluphenazine. Precision results, expressed by the intra-day and the inter-day relative standard deviation values, were good, being lower than 3.9%. Accuracy data were satisfactory as well.The method has been successfully applied to the analysis of drug plasma levels of psychiatric patients undergoing therapy with selected phenothiazines.     

Monolayers as models for supported catalysts: zirconium phosphonate films containing manganese(III) porphyrins

Organized monolayer films of a manganese tetraphenylporphyrin have been prepared and used as supported oxidation catalysts. Manganese 5,10,15,20-tetrakis(tetrafluorophenyl-4'-octadecyloxyphosphonic acid) porphyrin (1) has been immobilized as a monolayer film by a combination of Langmuir-Blodgett (LB) and self-assembled monolayer techniques that use zirconium phosphonate linkages to bind the molecule to the surface. Analysis by FTIR, XPS, UV-vis and polarized optical spectroscopy show that the films consist of noninteracting molecules effectively anchored and oriented nearly parallel to the surface. The monolayer films are stable to the solvent and temperature conditions needed to explore organic oxidations. The activity of films of 1 toward the epoxidation of cyclooctene using iodosylbenzene as the oxidant was compared to that of Manganese 5,10,15,20-tetrakis(pentafluorophenyl) porphyrin (2) and 1 under equivalent homogeneous conditions. The immobilized porphyrin 1 shows an enhanced activity relative to either homogeneous reaction. The main difference between 1 and 2 is the four alkyl phosphonate arms in 1 designed to incorporate the porphyrin within the films. The increased activity of immobilized 1 is a combination of the porphyrin structure, which prohibits the formation of mu-oxo dimers even in solution, and a change in conformation when anchored to the surface. The study demonstrates that careful monolayer studies can provide useful models for the design and study of supported molecular catalyst systems.     

MOF thin films: existing and future applications

The applications and potentials of thin film coatings of metal-organic frameworks (MOFs) supported on various substrates are discussed in this critical review. Because the demand for fabricating such porous coatings is rather obvious, in the past years several synthesis schemes have been developed for the preparation of thin porous MOF films. Interestingly, although this is an emerging field seeing a rapid development a number of different applications on MOF films were either already demonstrated or have been proposed. This review focuses on the fabrication of continuous, thin porous films, either supported on solid substrates or as free-standing membranes. The availability of such two-dimensional types of porous coatings opened the door for a number of new perspectives for functionalizing surfaces. Also for the porous materials themselves, the availability of a solid support to which the MOF-films are rigidly (in a mechanical sense) anchored provides access to applications not available for the typical MOF powders with particle sizes of a few μm. We will also address some of the potential and applications of thin films in different fields like luminescence, QCM-based sensors, optoelectronics, gas separation and catalysis. A separate chapter has been devoted to the delamination of MOF thin films and discusses the potential to use them as free-standing membranes or as nano-containers. The review also demonstrates the possibility of using MOF thin films as model systems for detailed studies on MOF-related phenomena, e.g. adsorption and diffusion of small molecules into MOFs as well as the formation mechanism of MOFs (101 references).     

Combining colloidal probe atomic force and reflection interference contrast microscopy to study the compressive mechanics of hyaluronan brushes

We describe a method that combines colloidal probe atomic force microscopy (AFM) and reflection interference contrast microscopy (RICM) to characterize the mechanical properties of thin and solvated polymer films. When analyzing polymer films, a fundamental problem in colloidal probe AFM experiments is to determine the distance at closest approach between the probe and the substrate on which the film is deposited. By combining AFM and RICM in situ, forces and absolute distances can be measured simultaneously. Using the combined setup, we quantify the compressive mechanics of films of the polysaccharide hyaluronan that is end-grafted to a supported lipid bilayer. The experimental data, and comparison with polymer theory, show that hyaluronan films are well-described as elastic, very soft and highly solvated polymer brushes. The data on these well-defined films should be a useful reference for the investigation of the more complex hyaluronan-rich coats that surround many living cells.     

Homogeneous liquid crystal alignment on poly(vinylidene fluoride-trifluoroethylene) films subjected to ion-beam irradiation

We demonstrate homogeneous and uniform liquid crystal (LC) alignment on poly(vinylidene fluoride-trifluoroethylene) [PVDF-TrFE] films using ion-beam (IB) irradiation and a performance improvement of twisted nematic (TN) cells using IB-irradiated PVDF-TrFE films. Spontaneous ferroelectricity of the PVDF-TrFE films was modified by IB irradiation, which affected the LC alignment properties. The variation in the pre-tilt angles of the LC molecules on the IB-irradiated PVDF films is attributed to surface reformation, including defluorination and oxidation because the pre-tilt angles of LC molecules can be controlled by adjusting the fluorine content. The results of contact angle measurements supported this phenomenon. A 58% reduction in the switching voltage was observed for TN cells, indicating that the IB-irradiated PVDF-TrFE films are a promising candidate for use as an alignment layer.     

Reaction pathways for ethanol on model Co/ZnO(0001) catalysts

The pathways for the reaction of ethanol on model catalysts consisting of Co and CoO films and particles supported on single crystal ZnO(0001) surfaces were studied using X-ray Photoelectron Spectroscopy (XPS) and Temperature Programmed Desorption (TPD). On supported metallic Co films and particles ethanol was found to primarily undergo decarbonylation forming CO, H(2), and adsorbed methyl groups. In contrast, supported CoO particles were found to be largely unreactive toward ethanol. High selectivity to the dehydrogenation product, acetaldehyde, was only observed when the supported Co was partially oxidized and contained both Co(0) and Co(2+). Since acetaldehyde is thought to be a critical intermediate during steam reforming of ethanol (SRE) to produce H(2) and CO(2), the results of this study suggest that partially oxidized Co species provide the active sites for this reaction. This result is consistent with studies of high surface area Co/ZnO catalysts which also suggest that both Co(0) and Co(2+) species are present under typical SRE reaction conditions.     

Silica colloidal crystals as three-dimensional scaffolds for supported lipid films

This report describes the assembly of laterally diffusive lipid layers within the pores of colloidal crystals for potential application in membrane-based sensing. The amount of lipid encapsulated within colloidal crystals depends upon the method used to introduce the lipid to the crystalline substrate. Relative to a planar supported lipid bilayer, lipid loading in a 6.6 microm thick crystal was 15-73 times greater, as observed by fluorescence microscopy. Protein adsorption studies indicate that the crystal pores are open and that the silica surface of the crystal is passivated with respect to adsorption of a model protein when coated with POPC. Furthermore, the mesoporous environment of the colloidal crystal is found to protect lipid films from drying and rehydration processes that destroy planar supported lipid bilayers. The potential of colloidal crystal encapsulated lipid films for chemical sensing is demonstrated by a model protein binding assay.     

Infrared spectroscopy of competitive interactions between liquid crystals, metal salts, and dimethyl methylphosphonate at surfaces

We report the use of Fourier transform polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) to characterize the influence of dimethyl methylphosphonate (DMMP) on the molecular interactions occurring within thin films of nitrile-containing liquid crystals supported on surfaces presenting metal perchlorate salts. Infrared spectra obtained using thin films of 4'-octyl-4-biphenylcarbonitrile (8CB) supported on copper(II) perchlorate salts reveal the nitrile groups of 8CB to be coordinated to the copper(II) on these surfaces, and subsequent exposure of the system to DMMP to result in the elimination of these coordinated nitrile groups. Concurrently, evidence of coordination of the phosphoryl group of DMMP with copper(II) is provided by measurement of a shift of the phosphoryl stretch from 1246 to 1198 cm(-1). In contrast, surfaces presenting nickel(II) perchlorate salts only weakly coordinate with DMMP [the phosphoryl peak shifts from 1246 to 1213 cm(-1) in the presence of nickel(II)], and exposure of 8CB to DMMP results in only partial loss of coordination of the nitrile groups of 8CB with nickel(II). These PM-IRRAS measurements and others reported in this article provide insights into the molecular origins of macroscopic ordering transitions that are observed when micrometer-thick films of nitrile-containing liquid crystals supported on copper(II) or nickel(II) perchlorate are exposed to DMMP: Upon exposure to DMMP, nematic phases of 4'-pentyl-4-biphenylcarbonitrile (5CB) supported on copper(II) perchlorate salts undergo ordering transitions, whereas 5CB supported on nickel(II) perchlorate salts do not. Our IR results support the hypothesis that these ordering transitions reflect the relative strengths of coordination interactions occurring between the 5CB, DMMP, and the metal salts at these interfaces.     

A structural study of amphiphilic PAMAM (poly(amido amine)) dendrimers in Langmuir and Langmuir-Blodgett films

Two amphiphilic PAMAM dendrimers are synthesized by attaching 12-hydroxydodecanoic acid (HA) chains to a poly(amido amine) (PAMAM) dendrimer core (including generation I and generation II). The limiting molecular area obtained from the surface pressure-area isotherm at the air/water interface suggests the edge-on configuration for both dendrimers in Langmuir films. The edge-on arrangement is also supported by the atomic force microscopic (AFM) studies of the Langmuir-Blodgett films.