Photodegradation assessment of amisulpride, doxepin, haloperidol, risperidone, venlafaxine, and zopiclone in bulk drug and in the presence of excipients

Photostability of amisulpride, doxepin, haloperidol, risperidone, venlafaxine, and zopiclone in APIs and powdered tablets during exposure to UVA irradiation was studied. In order to evaluate the photodegradation process an ultrahigh performance liquid chromatography method coupled with tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. It was found that the photodegradation of the studied compounds depends on the type of drug and co-existing excipients. Different percentage of photodegradation of the studied drugs was observed, and therefore amisulpride decomposed at 2.63% in bulk drug and at 5.74% in pharmaceutical preparation, doxepin: 29% and 72.38%, haloperidol: 3.71% and 26.20%, risperidone: 7.13% and 12.86%, venlafaxine: 38.59% and 4.22%, zopiclone: 18.62% and 31.42% respectively, after 114 days of UVA irradiation. In addition, kinetic evaluation of the photodegradation process was performed by determining the order of reaction, reaction rate constant k and time $t_{0.1}$ and $t_{0.5}$. The photodegradation products of studied drugs were identified, and their fragmentation pathways, derived from MS/MS data, were proposed. The photostability testing is an integral part of the drug stability assessment to ensure quality, efficacy and safety of the formulated products during manufacturing process, storage as well as normal use

Voltammetric determination of trace elements (Cu, Pb, Zn) in peloid-based pharmaceuticals

The research on the potential health risk posed to consumers by toxic elements that can be found in peloids is still lacking. Moreover, in Polish law no clinical or pharmacological tests are required to identify healing properties of peloids. The objective of this work was to determine some mineral content in selected peloids used in medical treatment. Anodic stripping voltammetry with differential pulse step was used for zinc, copper and lead determination. Decomposition of organic matrix was conducted by a simple wet digestion procedure using acid digestion vessel. Obtained results showed that proposed methods were suitable for the determination of investigated metallic elements. Lead content varied between 0.18 mg/kg (in MaúÊ Borowinowa) and reached up to 15.5 mg/kg of dry weight for Chokrak peloid. Zinc content ranged from 0.64 to 66.87 mg/kg and copper content was between 0.57 and 7.50 mg/kg. The proposed method was validated, the recovery for peloid samples were 94 ñ 102%; 92 ñ 97%; 96 ñ 106% for copper, zinc and lead, respectively

Development and validation of stability-indicating HPLC methods for the estimation of lomefloxacin and balofloxacin oxidation process under ACVA, H2O2H_{2}O_{2} or KMnO4KMnO_{4} treatment. Kinetic evaluation and identification of degradation products by mass spectrometry

The oxidation of lomefloxacin (LOM) and balofloxacin (BAL) under the influence of azo initiator of radical reactions of 4,4′-azobis(4-cyanopentanoic acid) (ACVA) and H2O2 was examined. Oxidation using H2O2 was performed at room temperature while using ACVA at temperatures: 40, 50, 60 °C. Additionally, the oxidation process of BAL under the influence of KMnO4 in an acidic medium was investigated. New stability-indicating HPLC methods were developed in order to evaluate the oxidation process. Chromatographic analysis was carried out using the Kinetex 5u XB—C18 100A column, Phenomenex (Torrance, CA, USA) (250 × 4.6 mm, 5 μm particle size, core shell type). The chromatographic separation was achieved while using isocratic elution and a mobile phase with the composition of 0.05 M phosphate buffer (pH = 3.20 adjusted with o-phosphoric acid) and acetonitrile (87:13 v/v for LOM; 80:20 v/v for BAL). The column was maintained at 30 °C. The methods were validated according to the ICH guidelines, and it was found that they met the acceptance criteria. An oxidation process followed kinetics of the second order reaction. The most probable structures of LOM and BAL degradation products formed were assigned by the UHPLC/MS/MS method

Zinc and propolis reduces cytotoxicity and proliferation in skin fibroblast cell culture : total polyphenol content and antioxidant capacity of propolis

It has been demonstrated that zinc exerts its beneficial influence on skin fibroblasts. Propolis, a complex mixture of plant-derived and bees’ products, was reported to stimulate cicatrization processes in skin and prevent infections. The aim of this study was to find out how zinc and propolis influence human skin fibroblasts in cell culture and to compare the effect of individual compounds to the effect of a mixture of zinc and propolis. In this study, zinc, as zinc aspartate, at a concentration of 16 μM, increased human fibroblasts proliferation in cell culture, whereas propolis at a concentration of 0.01 % (w/v) revealed antiproliferative and cytotoxic action followed by mild cell necrosis. In culture, zinc was effectively transported into fibroblasts, and propolis inhibited the amount of zinc incorporated into the cells. An addition of propolis to the medium caused a decrease in the Zn(II) amount incorporated into fibroblasts. The obtained results also indicate an appreciable antioxidant property of propolis and revealed its potential as a supplement when applied at doses lower than 0.01 % (w/v). In conclusion, the present study showed that zinc had a protective effect on human cultured fibroblasts’ viability, although propolis revealed its antiproliferative action and caused mild necrosis

Optimization of method for zinc analysis in several bee products on renewable mercury film silver based electrode

Zinc is an interesting target for detection as it is one of the elements necessary for the proper functioning of the human body, its excess and deficiency can cause several symptoms. Several techniques including electrochemistry have been developed but require laboratory equipment, preparative steps and mercury or complex working electrodes. We here described the development of a robust, simple and commercially available electrochemical system. Differential pulse (DP) voltammetry was used for this purpose with the cyclic renewable mercury film silver based electrode (Hg(Ag)FE) and 0.05 M KNO3 solution as a supporting electrolyte. The effect of various factors such as: preconcentration potential and time, pulse amplitude and width, step potential and supporting electrolyte composition are optimized. The limits of detection (LOD) and quantification (LOQ) were 1.62 ng/mL and 4.85 ng/mL, respectively. The repeatability of the method at a concentration level of the analyte as low as 3 ng/mL, expressed as RSD is 3.5% (n = 6). Recovery was determined using certified reference material: Virginia Tobacco Leaves (CTA-VTL-2). The recovery of zinc ranged from 96.6 to 106.5%. The proposed method was successfully applied for determination of zinc in bee products (honey, propolis and diet supplements) after digestion procedure

Semiautomatic and fully functional electrochemical microanalyzer BO-05 suitable for scientific, didactic, and analytical applications : the use in the potentiometric analysis of drugs

This article presents the potentiometric method of determination of chlorides using the original BO-05 electrochemical microanalyzer. The quantification of chlorides is one of the frequently performed methods, both in the indirect determination of active pharmaceutical ingredients (API) and impurities in pharmaceutical raw materials, pharmacopoeial substances or pharmaceutical formulations as well. Successfully validated method was used to the analysis of chlorides in the preparations containing verapamil hydrochloride in form of tablets Staveran® and Verapamil® . The mean content of the studied API calculated to one tablet was close to the declared and equal to 123.6±1.5 mg and 122.6±1.1 mg, respectively. The presence of excipients have no significant impact on the final results. Thus shown that the electrochemical microanalyzer BO-05 is suitable for scientific, didactic and analytical applications

Semiautomatic and fully functional electrochemical microanalyzer BO-05 suitable for scientific, didactic, and analytical applications: The use in the potentiometric analysis of drugs

This article presents the potentiometric method of determination of chlorides using the original BO-05 electrochemical microanalyzer. The quantification of chlorides is one of the frequently performed methods, both in the indirect determination of active pharmaceutical ingredients (API) and impurities in pharmaceutical raw materials, pharmacopoeial substances or pharmaceutical formulations as well. Successfully validated method was used to the analysis of chlorides in the preparations containing verapamil hydrochloride in form of tablets Staveran® and Verapamil®. The mean content of the studied API calculated to one tablet was close to the declared and equal to 123.6±1.5 mg and 122.6±1.1 mg, respectively. The presence of excipients have no significant impact on the final results. Thus shown that the electrochemical microanalyzer BO-05 is suitable for scientific, didactic and analytical applications

Development and verification of new solid dental filling temporary materials containing zinc : formula development stage

Caries is the most popular problem affecting teeth and this is the reason why so many temporary dental filling materials are being developed. An example of such filling is zinc oxide paste mixed with eugenol, Thymodentin and Coltosol FÆ. Zinc-oxide eugenol is used in dentistry because of its multiplied values: it improves heeling of the pulp by dentine bridge formation; has antiseptic properties; is hygroscopic. Because of these advantages compouds of zinc oxide are used as temporary fillings, especially in deep caries lesions when treatment is oriented on support of vital pulp. Temporary dental fillings based on zinc oxide are prepared ex tempore by simple mixing powder (Thymodentin) and eugenol liqiud together or a ready to use paste Coltosol FÆ. Quantitative composition depends mainly on experience of person who is preparing it, therefore, exact qualitative composition of dental fillings is not replicable. The main goal of the study was to develop appropriate dental fillings in solid form containing set amount of zinc oxide. Within the study, the influence of preparation method on solid dental fillings properties like mechanical properties and zinc ions release were examined

Chronic treatment with zinc and antidepressants induces enhancement of presynaptic/extracellular zinc concentration in the rat prefrontal cortex

Zinc exhibits antidepressant-like activity in preclinical tests/models. Moreover, zinc homeostasis is implicated in the pathophysiology of affective disorders. The aim of the present study was to examine the effect of chronic zinc, citalopram and imipramine intraperitoneal administration on the presynaptic and extracellular zinc concentration in the rat prefrontal cortex and hippocampus. We used two methods: zinc–selenium histochemistry (which images the pool of presynaptic-vesicle zinc) and anodic stripping voltammetry (ASV) for zinc determination in microdialysate (which assays the extracellular zinc concentration). We report that chronic (14×) zinc (hydroaspartate, 10 and 65 mg/kg) and citalopram (20 mg/kg) administration increased the pool of presynaptic zinc (by 34, 50 and 37%, respectively) in the rat prefrontal cortex. The 21% increase induced by imipramine (20 mg/kg) was marginally significant. Likewise, zinc (hydroaspartate, 65 mg/kg), citalopram and imipramine increased the extracellular zinc (although with a different pattern: time point, area under the curve and/or basal level) in this brain region. Furthermore, zinc induced an increase in presynaptic (by 65%) and extracellular zinc (by 90%) in the hippocampus, while both citalopram and imipramine did not. These results indicate that all of the treatments increase presynaptic/extracellular zinc concentrations in the rat prefrontal cortex, which may then contribute to their antidepressant mechanisms. Alterations induced by zinc (but not antidepressants) administration in the hippocampus may be related to specific zinc mechanisms. All the data (previous and present) on the effect of antidepressant treatments on the presynaptic/extracellular zinc concentrations suggest the involvement of this biometal presynaptic/synaptic homeostasis in the antidepressant mechanism(s)