scholarly journals Metoprolol and Its Degradation and Transformation Products Using AOPs—Assessment of Aquatic Ecotoxicity Using QSAR

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3102
Author(s):  
Melanie Voigt ◽  
Indra Bartels ◽  
Dorothee Schmiemann ◽  
Lars Votel ◽  
Kerstin Hoffmann-Jacobsen ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
High Performance ◽  
Degradation Products ◽  
Sewage Treatment ◽  
Transformation Products ◽  
Quantitative Structure Activity Relationship ◽  
Secondary Products ◽  
Structural Isomers ◽  
Qsar Analysis ◽  
Accelerated Degradation

Pharmaceuticals are found in waterbodies worldwide. Conventional sewage treatment plants are often not able to eliminate these micropollutants. Hence, Advanced Oxidation Processes (AOPs) have been heavily investigated. Here, metoprolol is exposed to UV irradiation, hydrogen peroxide, and ozonation. Degradation was analyzed using chemical kinetics both for initial and secondary products. Photo-induced irradiation enhanced by hydrogen peroxide addition accelerated degradation more than ozonation, leading to complete elimination. Degradation and transformation products were identified by high-performance liquid-chromatography coupled to high-resolution higher-order mass spectrometry. The proposed structures allowed to apply Quantitative Structure-Activity Relationship (QSAR) analysis to predict ecotoxicity. Degradation products were generally associated with a lower ecotoxicological hazard to the aquatic environment according to OECD QSAR toolbox and VEGA. Comparison of potential structural isomers suggested forecasts may become more reliable with larger databases in the future.

scholarly journals Lomefloxacin—Occurrence in the German River Erft, Its Photo-Induced Elimination, and Assessment of Ecotoxicity

2020 ◽  
Vol 2 (1) ◽  
pp. 74-90 ◽  
Author(s):  
Melanie Voigt ◽  
Benjamin Hentschel ◽  
Nina Theiss ◽  
Christina Savelsberg ◽  
Indra Bartels ◽  
...  
Keyword(s):  
Irradiation Time ◽  
Transformation Products ◽  
Quantitative Structure Activity Relationship ◽  
The Novel ◽  
Qsar Analysis ◽  
Water Matrix ◽  
Kinetic Rate Constants ◽  
Time Required ◽  
Far Ultraviolet ◽  
Uvc Radiation

Pharmaceuticals in waters represent a worldwide problem of today. Advanced oxidation processes (AOPs) are being researched for elimination of the ecological hazard. Among the substances, the fluoroquinolone antibiotic lomefloxacin was selected for investigation in this study. Lomefloxacin (LOM) was found in the German river Erft. Near and far ultraviolet (UVA, UVC) radiation were used as AOPs and compared for efficiency depending on pH, water matrix, and catalysts. Chemical kinetics description revealed that UVC at pH 8–9 led to the fastest degradation of LOM. The catalysts hydrogen peroxide and titanium dioxide had only limited influence on the degradation rate. Seven novel transformation products were structurally identified by high-resolution higher-order mass spectrometry. Ecotoxicity of the novel and known compounds was assessed by quantitative structure-activity relationship (QSAR) analysis. In addition, irradiation time dependent minimal, and half-maximal inhibitory concentrations (MIC, IC50) of LOM solutions were determined and suggested as ecotoxicological hazard indicators. From MIC and kinetic rate constants, the irradiation time required for compound and activity removal could be predicted.

scholarly journals Prediction Model of Aryl Hydrocarbon Receptor Activation by a Novel QSAR Approach, DeepSnap–Deep Learning

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1317 ◽  
Author(s):  
Yasunari Matsuzaka ◽  
Takuomi Hosaka ◽  
Anna Ogaito ◽  
Kouichi Yoshinari ◽  
Yoshihiro Uesawa
Keyword(s):  
Deep Learning ◽  
Aryl Hydrocarbon Receptor ◽  
High Performance ◽  
Prediction Models ◽  
Chemical Activation ◽  
Quantitative Structure Activity Relationship ◽  
Receptor Activation ◽  
Superior Performance ◽  
Qsar Analysis ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that senses environmental exogenous and endogenous ligands or xenobiotic chemicals. In particular, exposure of the liver to environmental metabolism-disrupting chemicals contributes to the development and propagation of steatosis and hepatotoxicity. However, the mechanisms for AhR-induced hepatotoxicity and tumor propagation in the liver remain to be revealed, due to the wide variety of AhR ligands. Recently, quantitative structure–activity relationship (QSAR) analysis using deep neural network (DNN) has shown superior performance for the prediction of chemical compounds. Therefore, this study proposes a novel QSAR analysis using deep learning (DL), called the DeepSnap–DL method, to construct prediction models of chemical activation of AhR. Compared with conventional machine learning (ML) techniques, such as the random forest, XGBoost, LightGBM, and CatBoost, the proposed method achieves high-performance prediction of AhR activation. Thus, the DeepSnap–DL method may be considered a useful tool for achieving high-throughput in silico evaluation of AhR-induced hepatotoxicity.

The Influence of Some Factors on Spirolactone Stability in Solution

2008 ◽  
Vol 59 (7) ◽  
Author(s):  
Daniela Lucia Muntean ◽  
Silvia Imre ◽  
Cosmina Voda
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Uv Irradiation ◽  
High Performance ◽  
Degradation Products ◽  
Simultaneous Action ◽  
Ethanolic Solution ◽  
Degradation Processes ◽  
Stable Solutions ◽  
Preformulation Study

The influence of some factors on spironolactone stability in solution was studied, by applying high-performance liquid chromatography, as a part of a pharmaceutical preformulation study in order to obtain a spironolactone solution for alopecia treatment. Solutions of 1 mg/ml spironolactone in aqueous ethanolic solution 1 : 1 and in 20 mM cyclodextrines solutions (b-, hydroxi-b- and methyl-b-cyclodextrine) was used, maintained at 8 and 22 �C, protected from light and after UV irradiation at 254 nm. The main degradation products were 7a-thiospirolactone and canrenone. The most stable solutions were the alcoholic ones and with methyl-beta-cyclodextrine, but the simultaneous action of temperature and UV irradiation allowed degradation processes after one hour of exposure, more aggressive in the presence of methyl-beta-cyclodextrine. In conclusion, for alopecia treatment with spironolactone a 1 mg/mL ethanolic solution could be used and it is recommendable the protection of treated zone.

In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests

2018 ◽  
Vol 21 (4) ◽  
pp. 262-270 ◽  
Author(s):  
Zehao Huang ◽  
Na Li ◽  
Kaifeng Rao ◽  
Cuiting Liu ◽  
Zijian Wang ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
A549 Cells ◽  
Quantitative Structure Activity Relationship ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Effects ◽  
Qsar Analysis ◽  
Cell Assays ◽  
Micronucleus Tests ◽  
Damaging Effects

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

Recent Applications of High Performance Thin Layer Chromatography and Derivative Spectrophotometry in Pharmaceutical Analysis

2020 ◽  
Vol 16 (6) ◽  
pp. 671-689
Author(s):  
Marcin Gackowski ◽  
Marcin Koba ◽  
Katarzyna Mądra-Gackowska ◽  
Piotr Kośliński ◽  
Stefan Kruszewski
Keyword(s):  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Pharmaceutical Analysis ◽  
High Performance ◽  
Degradation Products ◽  
Derivative Spectrophotometry ◽  
Accuracy And Precision ◽  
Post Marketing ◽  
Layer Chromatography

At present, no one can imagine drug development, marketing and post-marketing without rigorous quality control at each stage. Only modern, selective, accurate and precise analytical methods for determination of active compounds, their degradation products and stability studies are able to assure the appropriate amount and purity of drugs administered every day to millions of patients all over the world. For routine control of drugs simple, economic, rapid and reliable methods are desirable. The major focus of current scrutiny is placed on high-performance thin layer chromatography and derivative spectrophotometry methods, which fulfill routine drug estimation’s expectations [1-4]. The present paper reveals state-of-the-art and possible applications of those methods in pharmaceutical analysis between 2010 and 2018. The review shows advantages of high-performance thin layer chromatography and derivative spectrophotometry, including accuracy and precision comparable to more expensive and time-consuming methods as well as additional fields of possible applications, which contribute to resolving many analytical problems in everyday laboratory practice.

ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

2020 ◽  
Vol 16 (8) ◽  
pp. 1106-1112
Author(s):  
Ibrahim A. Darwish ◽  
Nasr Y. Khalil ◽  
Mohammad AlZeer
Keyword(s):  
High Performance ◽  
Kinase Inhibitor ◽  
Degradation Products ◽  
Internal Standard ◽  
Dosage Forms ◽  
Uv Detector ◽  
Stability Indicating ◽  
Therapeutic Benefits ◽  
Relative Standard

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

Validated Stability Indicating HPTLC Method for the Estimation of Amoxapine in Different Stress Conditions

2019 ◽  
Vol 15 (3) ◽  
pp. 273-279
Author(s):  
Shweta G. Rangari ◽  
Nishikant A. Raut ◽  
Pradip W. Dhore
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Analysis Data ◽  
Peak Height ◽  
Good Resolution ◽  
Stability Indicating ◽  
Limit Of Quantitation ◽  
Wide Range ◽  
Hptlc Method

Background:The unstable and/or toxic degradation products may form due to degradation of drug which results into loss of therapeutic activity and lead to life threatening condition. Hence, it is important to establish the stability characteristics of drug in various conditions such as in temperature, light, oxidising agent and susceptibility across a wide range of pH values.Introduction:The aim of the proposed study was to develop simple, sensitive and economic stability indicating high performance thin layer chromatography (HPTLC) method for the quantification of Amoxapine in the presence of degradation products.Methods:Amoxapine and its degraded products were separated on precoated silica gel 60F254 TLC plates by using mobile phase comprising of methanol: toluene: ammonium acetate (6:3:1, v/v/v). The densitometric evaluation was carried out at 320 nm in reflectance/absorbance mode. The degradation products obtained as per ICH guidelines under acidic, basic and oxidative conditions have different Rf values 0.12, 0.26 and 0.6 indicating good resolution from each other and pure drug with Rf: 0.47. Amoxapine was found to be stable under neutral, thermal and photo conditions.Results:The method was validated as per ICH Q2 (R1) guidelines in terms of accuracy, precision, ruggedness, robustness and linearity. A good linear relationship between concentration and response (peak area and peak height) over the range of 80 ng/spot to 720 ng/spot was observed from regression analysis data showing correlation coefficient 0.991 and 0.994 for area and height, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) for area were found to be 1.176 ng/mL and 3.565 ng/mL, whereas for height, 50.063 ng/mL and 151.707 ng/mL respectively.Conclusion:The statistical analysis confirmed the accuracy, precision and selectivity of the proposed method which can be effectively used for the analysis of amoxapine in the presence of degradation products.

Synthesis of New N1Arylpiperazine Substituted Xanthine Derivatives and Evaluation of their Antioxidant and Cytotoxic Effects

2019 ◽  
Vol 19 (4) ◽  
pp. 528-537 ◽  
Author(s):  
Lily Andonova ◽  
Iva Valkova ◽  
Dimitrina Zheleva-Dimitrova ◽  
Maya Georgieva ◽  
Georgi Momekov ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Structural Parameters ◽  
Leukemia Cell ◽  
Quantitative Structure Activity Relationship ◽  
Cytotoxic Effects ◽  
Qsar Analysis ◽  
Xanthine Derivatives ◽  
Human T Cell ◽  
Human Acute Myeloid Leukemia ◽  
Dye Reduction

Background: Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012, with most of the clinically used drugs being ineffective. Methylxanthines have raised more interest in research on modifying their structure because of their diverse biological activity. In addition, the piperazine nucleus is one of the most important heterocycles exhibiting remarkable pharmacological activities. Methods: The structure of the obtained compounds was characterized and elucidated by IR, 1H and 13C NMR and LCMS spectral analysis. The purity of the substances was proven by corresponding melting points and elemental analysis. The antioxidant activity was evaluated by four common methods – DPPH, ABTS, FRAP and lipid peroxidation assay. The cytotoxic effects of the tested series were evaluated using the standard MTT-dye reduction assay on three tumour cell lines. Results: A series of new xanthine derivatives comprising an arylpiperazine moiety at N1 were synthesized. The cytotoxicity against human T-cell leukemia cell SKW-3, human acute myeloid leukemia HL-60 and human Bcell precursor leukemia cell REH was evaluated. The relationship between the structure and citotoxicity of the compounds was investigated by quantitative structure-activity relationship (QSAR) analysis and the important structural parameters were drawn. Conclusion: The highest antioxidant activity was demonstrated by compound 6c. The highest cytotoxic effect was observed for compound 6f. It was found that cytotoxicity against SKW-3 depends on the electron density distribution in the structures. Branching of the molecular skeleton and introduction of heteroatoms like fluorine and sulfur in the structures also significantly improved the antiproliferative activity of the compounds.

scholarly journals Degradation Products of Polychlorinated Biphenyls and Their In Vitro Transformation by Ligninolytic Fungi

Toxics ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 81
Author(s):  
Kamila Šrédlová ◽  
Kateřina Šírová ◽  
Tatiana Stella ◽  
Tomáš Cajthaml
Keyword(s):  
Polychlorinated Biphenyls ◽  
Extracellular Enzymes ◽  
Degradation Products ◽  
Transformation Products ◽  
Irpex Lacteus ◽  
Chlorobenzoic Acid ◽  
Ligninolytic Fungi ◽  
Wide Range ◽  
Pcb Metabolites

Metabolites of polychlorinated biphenyls (PCBs)—hydroxylated PCBs (OH‑PCBs), chlorobenzyl alcohols (CB‑OHs), and chlorobenzaldehydes (CB‑CHOs)—were incubated in vitro with the extracellular liquid of Pleurotus ostreatus, which contains mainly laccase and low manganese-dependent peroxidase (MnP) activity. The enzymes were able to decrease the amount of most of the tested OH‑PCBs by > 80% within 1 h; the removal of more recalcitrant OH‑PCBs was greatly enhanced by the addition of the laccase mediator syringaldehyde. Conversely, glutathione substantially hindered the reaction, suggesting that it acted as a laccase inhibitor. Hydroxylated dibenzofuran and chlorobenzoic acid were identified as transformation products of OH‑PCBs. The extracellular enzymes also oxidized the CB‑OHs to the corresponding CB‑CHOs on the order of hours to days; however, the mediated and nonmediated setups exhibited only slight differences, and the participating enzymes could not be determined. When CB‑CHOs were used as the substrates, only partial transformation was observed. In an additional experiment, the extracellular liquid of Irpex lacteus, which contains predominantly MnP, was able to efficiently transform CB‑CHOs with the aid of glutathione; mono‑ and di-chloroacetophenones were detected as transformation products. These results demonstrate that extracellular enzymes of ligninolytic fungi can act on a wide range of PCB metabolites, emphasizing their potential for bioremediation.

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