Chemical Works of Gedeon Richter Plc

Budapest, Hungary

Chemical Works of Gedeon Richter Plc

Budapest, Hungary
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Beni Z.,Chemical Works of Gedeon Richter Plc. | Beni Z.,NMR Laboratory | Hada V.,Chemical Works of Gedeon Richter Plc. | Hada V.,MS Laboratory | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2012

In this review our aim is to look back on how the structure elucidation of bisindoles, especially with focus placed on vinblastine and vincristine analogues, has evolved alongside with the development of MS and NMR over the last 60 years from the perspective of our present-day use of state-of-the-art MS and NMR instrumentation and on the basis of our own accumulated views and experience in the field. © 2012 Elsevier B.V.

Gulyas B.,Karolinska Institutet | Vas A.,Chemical Works of Gedeon Richter Plc | Toth M.,Karolinska Institutet | Takano A.,Karolinska Institutet | And 5 more authors.
NeuroImage | Year: 2011

Backgrounds and purpose: The main objectives of the present study were (i) to measure density changes of activated microglia and the peripheral benzodiazepine receptor/translocator protein (TSPO) system during normal ageing in the human brain with positron emission tomography (PET) using the TSPO molecular imaging biomarker [11C]vinpocetine and (ii) to compare the level and pattern of TSPO in Alzheimer (AD) patients with age matched healthy subjects, in order to assess the biomarker's usefulness as a diagnostic imaging marker in normal (ageing) and pathological (AD) up-regulation of microglia. Methods and subjects: PET measurements were made in healthy volunteers, aged between 25 and 78years, and AD patients, aged between 67 and 82years, using [11C]vinpocetine as the tracer. Global and regional quantitative parameters of tracer uptake and binding, including time activity curves (TAC) of standard uptake values (%SUV), binding affinity parameters, intensity spectrum and homogeneity of the uptake distribution were measured and analysed. Results: Both %SUV and binding values increased with age linearly in the whole brain and in all brain regions. There were no significant differences between the %SUV values of the AD patients and age matched control subjects. There were, however, significant differences in %SUV values in a large number of brain regions between young subjects and old subjects, as well as young subjects and AD patients. The intensity spectrum analysis and homogeneity analysis of the voxel data show that the homogeneity of the %SUV values decreases with ageing and during the disease, whereas the centre of the intensity spectrum is shifted to higher %SUV values. These data indicate an inhomogeneous up-regulation of the TSPO system during ageing and AD. These changes were significant between the group of young subjects and old subjects, as well as young subjects and AD patients, but not between old subjects and AD patients. Conclusions: The present data indicate that [11C]vinpocetine may serve as a molecular imaging biomarker of the activity of the TSPO system and, consequently, of the up-regulation of microglia during ageing and in neuroinflammatory diseases. However, the global and regional brain %SUV values between AD patients and age matched controls are not different from each other. The disease specific changes, measured with [11C]vinpocetine in AD, are significantly different from those measured in age matched controls only if the inhomogeneities in the uptake pattern are explored with advanced mathematical techniques. For this reason, PET studies using [11C]vinpocetine, as molecular imaging biomarker, can efficiently visualise the activation of microglia and the up-regulation of TSPO during ageing and in diseased brains with the help of an appropriate inhomogeneity analysis of the radioligand's brain uptake pattern. © 2011 Elsevier Inc.

Gulyas B.,Karolinska Institutet | Toth M.,Karolinska Institutet | Vas A.,Chemical Works of Gedeon Richter Plc | Shchukin E.,Karolinska Institutet | And 3 more authors.
Current Radiopharmaceuticals | Year: 2012

With the main objective of comparing the prospective diagnostic power of two 11C-labelled molecular imaging biomarkers with affinity for TSPO and used for the visualisation of activated microglia after a stroke, we measured with positron emission tomography (PET) in four post-stroke patients the regional brain uptake and binding potential of [ 11C]vinpocetine and [ 11C]PK11195. Percentage standard uptake values (%SUV) and binding potential (BP ND) were used as outcome measures. The total peak brain uptake value and average global brain uptake value were higher for [ 11C]vinpocetine than for [ 11C]PK11195. The regional %SUV values were significantly higher for [ 11C]vinpocetine than for [ 11C]PK11195 in the hemispheres as well as in almost all standard brain regions. The %SUV values of [ 11C]vinpocetine were higher in the peri-infarct zone than in the ischaemic core, however, the difference did not prove to be significant. There was basically no difference in %SUV values between the ischaemic core and the peri-infarct zone for [ 11C]PK11195. The BP ND values for [ 11C]vinpocetine were higher in all standard regions than those for [ 11C]PK11195, but the difference was not significant between them. The BP ND values of [ 11C]vinpocetine were higher in the peri-infarct zone than in the ischaemic core, however, the difference did not prove to be significant. A comparative analysis of the two ligands indicates that [ 11C]vinpocetine shows a number of favourable characteristics over [ 11C]PK11195, but to demonstrate that it may serve as a prospective molecular imaging biomarker of microglia activation in post-stroke patients, further studies are required. © 2012 Bentham Science Publishers.

Dubrovay Z.,Chemical Works of Gedeon Richter Plc | Szalay P.G.,Eötvös Loránd University
Journal of Molecular Modeling | Year: 2014

Two-dimensional representation of a molecular structure is in some casesmisleading, since it may not correctly represent important details and may not provide adequate information on the electronic structure of the molecule. In such cases the physical-chemical properties of the molecule will not be properly interpreted on the basis of the molecular formula. For example, the NMR spectrum will differ significantly from what would be intuitively expected on the basis of this formula and one can deduce the correct electronic and steric structure of themolecule from the obtained spectra instead. In this article the NMR and quantum chemical analysis of the title compound 3-(2-methly-2- phenylhydrazinyl)cyclohex-2-en-1-one will be presented. The unusual NMR spectra and surprising protonation site of this compound will be explained based on the delocalization of the π-symmetric orbitals of its molecules. The proposed electronic structure and the observed but unexpected physical-chemical properties have been confirmed by quantum chemical calculations. © Springer-Verlag 2014.

Berta R.,Chemical Works of Gedeon Richter Plc. | Babjak M.,Chemical Works of Gedeon Richter Plc. | Gazdag M.,Chemical Works of Gedeon Richter Plc.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

In the pharmaceutical industry fast and efficient separation techniques play an increasing role among analytical methods because the samples to be investigated grow both in complexity and number, and there is an increasing time pressure to complete the analysis. Reducing the analysis time without decreasing the efficiency is possible using higher pressures, elevated temperatures, smaller particle sizes, or a combination of these approaches. Recently developed chromatographic techniques such as the UHPLC (ultra high performance liquid chromatography) and HTLC (high temperature liquid chromatography) are highly promising in meeting these demands. In this study, high temperature liquid chromatography (HTLC) with a zirconia-based column and temperatures elevated up to 150 °C was used. We investigated the chromatographic behaviour of a steroid active pharmaceutical ingredient (levonorgestrel) and its structurally related impurities as model compounds. The effect of the temperature in the range of 50-150 °C and the flow-rate in the range of 0.5-3.0. ml/min, and using methanol as an organic modifier, were studied for optimisation of the separation method. © 2010 Elsevier B.V.

Gorog S.,Chemical Works of Gedeon Richter Plc.
TrAC - Trends in Analytical Chemistry | Year: 2015

Identification is an important step in the quality control of drugs and the research for new drugs. First, this review discusses the identification of bulk drugs and the active ingredients in formulations, based mainly on pharmacopoeial tests. The most important methods for this purpose are infrared (IR) and, to a lesser extent, ultraviolet (UV) spectroscopy, as well as retention matching with standards using high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). The identification of impurities and degradants is based mainly on HPLC-UV, HPLC-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) spectroscopies. The above methods are also used for identification purposes in drug research. The use of MS and NMR in the research for large-molecule drugs of biotechnological origin and natural products, mainly of plant origin, with special respect to traditional Chinese (and Indian) medicines is also discussed. The review concludes with the identification aspects of the fight against counterfeit drugs. © 2014.

Suba D.,Chemical Works of Gedeon Richter Plc | Urbanyi Z.,Chemical Works of Gedeon Richter Plc | Salgo A.,Budapest University of Technology and Economics
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2016

Capillary electrophoresis techniques are widely used in the analytical biotechnology. Different electrophoretic techniques are very adequate tools to monitor size—and charge heterogenities of protein drugs. Method descriptions and development studies of capillary zone electrophoresis (CZE) have been described in literature. Most of them are performed based on the classical one-factor-at-time (OFAT) approach. In this study a very simple method development approach is described for capillary zone electrophoresis: a “two-phase-four-step” approach is introduced which allows a rapid, iterative method development process and can be a good platform for CZE method. In every step the current analytical target profile and an appropriate control strategy were established to monitor the current stage of development. A very good platform was established to investigate intact and digested protein samples. Commercially available monoclonal antibody was chosen as model protein for the method development study. The CZE method was qualificated after the development process and the results were presented. The analytical system stability was represented by the calculated RSD% value of area percentage and migration time of the selected peaks (<0.8% and <5%) during the intermediate precision investigation. © 2016 Elsevier B.V.

Szilagyi G.,State Health Center | Vas A.,Chemical Works of Gedeon Richter Plc. | Kerenyi L.,Debrecen University | Nagy Z.,Semmelweis University | And 2 more authors.
Acta Neurologica Scandinavica | Year: 2012

Background- A common consequence of unilateral stroke is crossed cerebellar diaschisis (CCD), a decrease in regional blood flow (CBF) and metabolism (CMRglu) in the cerebellar hemisphere contralateral to the affected cerebral hemisphere. Former studies indicated a post-stroke time-dependent relationship between the degree of CCD and the clinical status of acute and sub-acute stroke patients, but no study has been performed in post-stroke patients. Objectives- The objective of this investigation was to evaluate the quantitative correlation between the degree of CCD and the values of clinical stroke scales in post-stroke patients. Materials and Methods- We measured with positron emission tomography (PET) regional CBF and CMRglu values in the affected cortical regions and the contralateral cerebellum in ten ischaemic post-stroke patients. Based on these quantitative parameters, the degree of diaschisis (DoD) was calculated, and the DoD values were correlated with three clinical stroke scales [Barthel Index, Orgogozo Scale and Scandinavian Neurological Scale (SNS)]. Results- There were significant linear correlations between all clinical stroke scales and the CCD values (Barthel Index and Orgogozo Scale: P<0.001, for both CBF and CMRglu; SNS: P=0.007 and P=0.044; CBF and CMRglu, respectively). Conclusions- The findings indicate that DoD can be used as a quantitative indicator of the functional impairments following stroke, i.e. it can serve as a potential surrogate of the severity of the damage. © 2011 John Wiley & Sons A/S.

Suba D.,Chemical Works of Gedeon Richter Plc | Urbanyi Z.,Chemical Works of Gedeon Richter Plc | Salgo A.,Budapest University of Technology and Economics
Journal of Pharmaceutical and Biomedical Analysis | Year: 2015

Capillary isoelectric focusing (cIEF) is a basic and highly accurate routine analytical tool to prove identity of protein drugs in quality control (QC) and release tests in biopharmaceutical industries. However there are some ". out-of-the-box" applications commercially available which provide easy and rapid isoelectric focusing solutions for investigating monoclonal antibody drug proteins. However use of these kits in routine testings requires high costs.A capillary isoelectric focusing method was developed and validated for identification testing of monoclonal antibody drug products with isoelectric point between 7.0 and 9.0. A method was developed providing good pH gradient for internal calibration (R2>0.99) and good resolution between all of the isoform peaks (R=2), minimizing the time and complexity of sample preparation (no urea or salt used). The method is highly reproducible and it is suitable for validation and method transfer to any QC laboratories. Another advantage of the method is that it operates with commercially available chemicals which can be purchased from any suppliers. The interaction with capillary walls (avoid precipitation and adsorption as far as possible) was minimized and synthetic isoelectric small molecular markers were used instead of peptide or protein based markers.The developed method was validated according to the recent ICH guideline (Q2(R1)). Relative standard deviation results were below 0.2% for isoelectric points and below 4% according to the normalized migration times. The method is robust to buffer components with different lot numbers and neutral capillaries with different type of inner coatings. The fluoro-carbon coated column was chosen because of costs-effectivity aspects. © 2015 Elsevier B.V.

Fekete S.,Budapest University of Technology and Economics | Olah E.,Chemical Works of Gedeon Richter Plc. | Fekete J.,Budapest University of Technology and Economics
Journal of Chromatography A | Year: 2012

Columns packed with sub-2 μm totally porous and sub-3 μm core-shell particles are very widespread nowadays to conduct fast and efficient separations. In order to carry out really fast separations, short (5. cm long) columns are very popular today. The goal of this paper is to review the recent possibilities in fast or "ultra-fast" HPLC by applying short and narrow bore columns packed with modern core-shell and very fine fully porous particles. Efficiency data obtained with these recently commercialized columns from the past few years are collected, discussed and compared in terms of potential separation time and efficiency. The reasons of the success of these columns are presented. This paper also shows that theoretically expected efficiency is sometimes compromised in practical work especially in the case of narrow bore columns. The extra-column dispersion of a given LC system can also dramatically decrease the performance of small columns. It is not possible to utilize the real efficiency of these small columns in spite of their really high intrinsic separation power. © 2011 Elsevier B.V.

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