RESUMEN
Determining the influence of environmental factors on the stability of drugs is very helpful when choosing excipients, storage conditions or packaging materials. In addition, information about possible toxic degradation products enables detecting and avoiding the harmful side effects of the drug. We used the thin-layer chromatographic-densitometric procedure for the assay of five coxibs, conducted degradation studies in various environments and at different temperatures along with the determination of pharmacokinetic parameters. The results were subjected to chemometric analysis, to investigate and visualize the similarities and differences of the studied coxibs. Samples of the tested drug were also analyzed by UPLC-MS/MS in order to identify degradation products, and determine possible drug degradation pathways. Using the human liver cancer HepG2 cell line, the hepatotoxic effect of the degradation products was also determined. It was observed that all substances were relatively stable under the analyzed conditions and degraded more in acidic than alkaline environments. Robenacoxib is the drug that decomposes the fastest, and cimicoxib turned out to be the most stable. Robenacoxib also showed significant hepatotoxicity at the highest tested concentration, which correlates with the high degree of its degradation, and the probable formation of a more hepatoxic product. The obtained mass spectra of compounds formed as a result of hydrolysis of the protonated drug leading to the formation of several product ions, which enabled us to propose probable degradation pathways.
RESUMEN
Considering the potential of nanostructured titanium dioxide layers as drug delivery systems, it is advisable to indicate the possibility of creating a functional drug delivery system based on anodic TiO2 for celecoxib as an alternative anti-inflammatory drug and its inclusion complex with ß-cyclodextrin. First, the optimal composition of celecoxib-ß-cyclodextrin complexes was synthesized and determined. The effectiveness of the complexation was quantified using isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR) nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM). Then, nanostructured titanium dioxide layers (TiO2) were synthesized using the electrochemical oxidation technique. The TiO2 layers with pore diameters of 60 nm and layer thickness of 1.60 µm were used as drug delivery systems. The samples were modified with pure celecoxib and the ß-cyclodextrin-celecoxib complex. The release profiles shown effective drug release from such layers during 24 h. After the initial burst release, the drug was continuously released from the pores. The presented results confirm that the use of nanostructured TiO2 as a drug delivery system can be effectively used in more complicated systems composed of ß-cyclodextrin-celecoxib complexes, making such drugs available for pain treatment, e.g., for orthopedic surgeries.
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Nowadays, the most important aspect related to the use of dietary supplements seems to be their quality. There are many reports indicating their insufficient quality primarily related to a much lower content of ingredients or even their absence. Currently, there is an increasing interest in supplementing the diet with various kinds of supplements, including those containing combinations of vitamins and minerals, among which preparations with vitamin D are very popular. This is probably due to the reduced production of this vitamin, depending on the amount of time spent in the sun and the use of UV-filters. Very often, preparations with cholecalciferol also contain vitamin K2, which is associated with their synergistic effect. Therefore, the question arises about the effectiveness of supplementation, which may be correlated with the quality of commonly available dietary supplements. In the presented work, it was undertaken to develop optimal conditions for the qualitative and quantitative determination of vitamins D2, D3 and K2 in dietary supplements available in various forms, using thin-layer chromatography with densitometric detection. As a result, the methodology for analyzing the content of three vitamins from various matrices was developed, optimized and validated in accordance with ICH requirements. The obtained results allow us to conclude that it is reliable and meets the requirements for analytical procedures used in the analysis of medicinal products. Based on the results obtained for examined dietary supplements, it can be stated that the amount of vitamin D3 in analyzed products is basically similar to that declared by the manufacturer, in contrast to vitamin K2, the content of which is diverse. The developed methodology seems to be a good, low-cost and quick way to control the quality of dietary supplements so that they can supplement the human diet and be a wholesome product.
Asunto(s)
Suplementos Dietéticos , Vitaminas , Humanos , Vitaminas/análisis , Suplementos Dietéticos/análisis , Vitamina A , Colecalciferol , Vitamina D , Control de Calidad , Vitamina KRESUMEN
Grapiprant is a new analgesic and anti-inflammatory drug belonging to the piprant class, approved in 2016 by the FDA Veterinary Medicine Center for the treatment of pain and inflammation associated with osteoarthritis in dogs. It acts as a highly selective antagonist of the EP4 receptor, one of the four prostaglandin E2 (PGE2) receptor subtypes. It has been shown to have anti-inflammatory effects in rat models of acute and chronic inflammation and clinical studies in people with osteoarthritis. The current state of knowledge suggests the possibility of using it in oncological therapy. The manuscript presents the development of conditions for the identification and quantitative determination of grapiprant by thin-layer chromatography with densitometric detection. The optimal separation of the substance occurs using silica gel 60F254 chromatographic plates and the mobile phase containing ethyl acetate-toluene-butylamine. Validation (according to ICH requirements) showed that the developed method is characterized by straightness of results in a wide concentration range with the limit of detection of 146.65 µg/mL. The %RSD values of the precision and accuracy confirm the sensitivity and reliability of the developed procedure. Next, the method was used for quantification of grapiprant in a pharmaceutical preparation, and for stability studies under various environmental conditions. Additionally, the mass studies were carried out on the stressed samples using the UPLC-MS/MS method. The degradation products were primarily characterized by comparing their mass fragmentation profiles with those of the drug. The results indicated a potential degradation pathway for grapiprant.
RESUMEN
Nowadays, topics related to the proper nutrition of the body, which requires a complex of compounds and supplementation of these ingredients have undoubtedly gained popularity, so it should come as no surprise that there is a widespread interest in vitamin D in science, medicine, analytics and nutrition. In the world of developing technologies, new directions of physiological action of this vitamin on the body are being discovered. Issues related to the demand for vitamin D in various populations and its sources in food, the appropriate form of supplementation, safety and toxicity are extremely important. The present manuscript focuses on the concise evaluation of key data in the field of vitamin D. Structure and physicochemical properties, demand and delivery trails, deficiency and its diagnosis, supplementation, interactions of vitamin D with supplements and drugs are discussed. Attention has also been paid to the methods of vitamin D analysis in various matrices, which allow for an accurate and precise quality assessment of dietary supplements, drugs and food products. The presented information allows deeper understanding of the mechanisms responsible for the development of many diseases in the context of vitamin D levels.