scholarly journals NanoUPLC-QTOF-MS/MS Determination of Major Rosuvastatin Degradation Products Generated by Gamma Radiation in Aqueous Solution

2021 ◽  
Vol 14 (11) ◽  
pp. 1160
Author(s):  
Lucija Dončević ◽  
Ema Svetličić ◽  
Amela Hozić ◽  
Branka Mihaljević ◽  
Dorota Jarmużek ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Free Radical ◽  
Gamma Radiation ◽  
Degradation Products ◽  
Gradient Elution ◽  
Degradation Pathway ◽  
Protective Role ◽  
Formation Mechanisms ◽  
Composition Analysis ◽  
Chemical Structures

Rosuvastatin, a member of the statin family of drugs, is used to regulate high cholesterol levels in the human body. Moreover, rosuvastatin and other statins demonstrate a protective role against free radical-induced oxidative stress. Our research aimed to investigate the end-products of free radical-induced degradation of rosuvastatin. To induce the radical degradation, an aqueous solution of rosuvastatin was irradiated using different doses of gamma radiation (50–1000 Gy) under oxidative conditions. Rosuvastatin and related degradation products were separated on nanoC18 column under gradient elution, and identification was carried out on hyphenated nanoUPLC and nanoESI-QTOF mass spectrometer system. Elemental composition analysis using highly accurate mass measurements together with isotope fitting algorithm identified nine major degradation products. This is the first study of gamma radiation-induced degradation of rosuvastatin, where chemical structures, MS/MS fragmentation pathways and formation mechanisms of the resulting degradation products are detailly described. The presented results contribute to the understanding of the degradation pathway of rosuvastatin and possibly other statins under gamma radiation conditions.

Nanouplc-Qtof-Ms/Ms Determination of Rosuvastatin Degradation Products Generated by Gamma Radiation in Aqueous Solution

2021 ◽  
Author(s):  
Lucija Dončević ◽  
Ema Svetličić ◽  
Amela Hozić ◽  
Dorota Jarmužek ◽  
Ivana Tartaro Bujak ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Gamma Radiation ◽  
Degradation Products

Validated RP-LC Methods for Investigation the Degradation Behavior of Acefylline: Application for Analysis in Two Binary Mixtures

2020 ◽  
Vol 16 ◽  
Author(s):  
Ola Mohamed EL-Houssini ◽  
Nagwan Hamdi Zawilla ◽  
Mohammad Abdul-Azim Mohammad
Keyword(s):  
Binary Mixtures ◽  
Degradation Products ◽  
Drug Product ◽  
Oxidative Degradation ◽  
Gradient Elution ◽  
Degradation Pathway ◽  
Ich Guidelines ◽  
Complete Study ◽  
Isocratic And Gradient Elution

Background: Acefylline (Acef) is a derivative of theophylline that has bronchodilator effects. Two binary mixtures were marketed for Acef: Acefylline piperazine/ Phenobarbitone (Acef-P/Phen) and Acefylline heptaminol/ Cinnarizine (Acef-H/ Cinn). To our knowledge none of the reported methods had the capacity to determine Acef in its binary mixture in presence of its degradation products and potential impurity theophylline (Theo). Methods: Two validated RP-LC methods were established for the determination of Acef-P/Phen and Acef-H/ Cinn in presence of Acef degradation products and its potential impurity Theo. A complete study of the forced acidic, alkaline and oxidative degradation of Acef was presented. The methods were based on LC separation on RP C18 columns using isocratic and gradient elution for Acef-P /Phen and Acef-H /Cinn mixtures, respectively. Different chromatographic conditions were examined and optimized. Results: Linear responses were attained over concentration ranges of 75-500/15-1000 μg/mL and 100-1000 /50- 500 μg/mL with mean percentage recoveries of (100.72±1.23)%/ (99.29±1.12)% and (100.44±1.27)%/ (99.01±0.97)% for Acef-P/Phen and Acef-H /Cinn, respectively. ICH guidelines were used for methods validation and all parameters were found to be acceptable. Conclusion: The methods showed to be accurate, precise and specific for the analysis of Acef-P/Phen and AcefH /Cinn in drug substance, drug product and in laboratory prepared mixtures in presence of Theo and up to 50% of degradation products. The structures of the main degradation products and the expected degradation pathway were suggested using the MS data.

The Inhibition of Platelet Aggregation by an Aorta Intima Extract

1974 ◽  
Vol 32 (02/03) ◽  
pp. 417-431 ◽  
Author(s):  
A. du P Heyns ◽  
D. J van den Berg ◽  
G. M Potgieter ◽  
F. P Retief
Keyword(s):  
Platelet Aggregation ◽  
Degradation Products ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Vascular Trauma ◽  
Wear And Tear ◽  
Sequential Addition ◽  
Aggregation Activity

SummaryThe platelet aggregating activity of extracts of different layers of the arterial wall was compared to that of Achilles tendon. Arterial media and tendon extracts, adjusted to equivalent protein content as an index of concentration, aggregated platelets to the same extent but an arterial intima extract did not aggregate platelets. Platelet aggregation induced by collagen could be inhibited by mixing with intima extract, but only to a maximum of about 80%. Pre-mixing adenosine diphosphate (ADP) with intima extracts diminished the platelet aggregation activity of the ADP. Depending on the relationship between ADP and intima extract concentrations aggregating activity could either be completely inhibited or inhibition abolished. Incubation of ADP with intima extract and subsequent separation of degradation products by paper chromatography, demonstrated a time-dependent breakdown of ADP with AMP, adenosine, inosine and hypoxanthine as metabolic products; ADP removal was complete. Collagen, thrombin and adrenaline aggregate platelets mainly by endogenous ADP of the release reaction. Results of experiments comparing inhibition of aggregation caused by premixing aggregating agent with intima extract, before exposure to platelets, and the sequential addition of first the intima extract and then aggregating agent to platelets, suggest that the inhibitory effect of intima extract results from ADP breakdown. It is suggested that this ADP degradation by intima extract may play a protective role in vivo by limiting the size of platelet aggregates forming at the site of minimal “wear and tear” vascular trauma.

scholarly journals Possible Protective Role of Melatonin in Pediatric Infectious Diseases and Neurodevelopmental Pathologies

2020 ◽  
Vol 10 (01) ◽  
pp. e104-e109
Author(s):  
Antonio Molina-Carballo ◽  
Antonio Emilio Jerez-Calero ◽  
Antonio Muñoz-Hoyos
Keyword(s):  
Endothelial Cell ◽  
Free Radical ◽  
Chronic Administration ◽  
Protective Role ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Energetic Metabolism ◽  
Beneficial Effects ◽  
Molecular Crosstalk

AbstractMelatonin, produced in every cell that possesses mitochondria, acts as an endogenous free radical scavenger, and improves energetic metabolism and immune function, by complex molecular crosstalk with other intracellular compounds. There is greatly increasing evidence regarding beneficial effects of acute and chronic administration of high melatonin doses, in infectious, developmental, and degenerative pathologies, as an endothelial cell and every cell protectant.

scholarly journals Characterization and Study on Fragmentation Pathways of a Novel Nerve Agent, ‘Novichok (A234)’, in Aqueous Solution by Liquid Chromatography–Tandem Mass Spectrometry

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1059
Author(s):  
Jin Young Lee ◽  
Kyoung Chan Lim ◽  
Hyun Suk Kim
Keyword(s):  
Mass Spectrometry ◽  
Aqueous Solution ◽  
Liquid Chromatography ◽  
Degradation Products ◽  
Aqueous Sample ◽  
Tandem Mass ◽  
Aqueous Samples ◽  
Fragmentation Pathways ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

As a first step toward studying the properties of Novichok (ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)), we investigated its degradation products and fragmentation pathways in aqueous solution at different pH levels by liquid chromatography–tandem mass spectrometry. A234 was synthesized in our laboratory and characterized by nuclear magnetic resonance spectroscopy. Three sets of aqueous samples were prepared at different pH levels. A stock solution of A234 was prepared in acetonitrile at a concentration of 1 mg/mL and stored at −20 °C until use. Aqueous samples (0.1 mg/mL) were prepared by diluting the stock solution with deionized water. The acidic aqueous sample (pH = 3.5) and basic aqueous sample (pH = 9.4) were prepared using 0.01 M acetic acid and 0.01 M potassium carbonate, respectively. The analysis of the fragmentation patterns and degradation pathways of A234 showed that the same degradation products were formed at all pH levels. However, the hydrolysis rate of A234 was fastest under acidic conditions. In all three conditions, the fragmentation pattern and the major degradation product of A234 were determined. This information will be applicable to studies regarding the decontamination of Novichok and the trace analysis of its degradation products in various environmental matrices.

Identification, Characterization, and Quantification of Impurities of Safinamide Mesilate: Process-Related Impurities and Degradation Products

2017 ◽  
Vol 100 (4) ◽  
pp. 1029-1037 ◽  
Author(s):  
Liang Zou ◽  
Lili Sun ◽  
Hui Zhang ◽  
Wenkai Hui ◽  
Qiaogen Zou ◽  
...  
Keyword(s):  
Degradation Products ◽  
Hplc Method ◽  
Formation Mechanisms ◽  
Stability Indicating ◽  
Related Impurities ◽  
Related Substances ◽  
Water Ph ◽  
Bulk Drug ◽  
First Time

Abstract The characterization of process-related impurities and degradation products of safinamide mesilate (SAFM) in bulk drug and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Four process-related impurities (Imp-B, Imp-C, Imp-D, and Imp-E) were found in the SAFM bulk drug. Five degradation products (Imp-A, Imp-C, Imp-D, Imp-E, and Imp-F) were observed in SAFM under oxidative conditions. Imp-C, Imp-D, and Imp-E were also degradation products and process-related impurities. Remarkably, one new compound, identified as (S)-2-[4-(3-fluoro-benzyloxy) benzamido] propanamide (i.e., Imp-D), is being reported here as an impurity for the first time. Furthermore, the structures of the aforementioned impurities were characterized and confirmed via IR, NMR, and MS techniques, and the most probable formation mechanisms of all impurities proposed according to the synthesis route. Optimum separation was achieved on an Inertsil ODS-3 column (250 × 4.6 mm, 5 μm), using 0.1% formic acid in water (pH adjusted to 5.0) and acetonitrile as the mobile phase in gradient mode. The proposed method was found to be stability-indicating, precise, linear, accurate, sensitive, and robust for the quantitation of SAFM and its process-related substances, including its degradation products.

A New, Rapid and Simple RP-HPLC Method for Stability Quantification of a Protease Inhibitor in Tablets

2021 ◽  
Author(s):  
Rochele Cassanta Rossi ◽  
Josué Guilherme Lisbôa Moura ◽  
Vanessa Mossmann ◽  
Patrícia Weimer ◽  
Pedro Eduardo Fröehlich
Keyword(s):  
Quality Control ◽  
Protease Inhibitor ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Array Detector ◽  
Forced Degradation ◽  
Control Analysis ◽  
Quality Control Laboratory ◽  
The Stability

Abstract Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control analysis of fosamprenavir-coated tablets. The purpose of the study was to develop and validate a method for determining the stability of fosamprenavir-coated tablets (Telzir®) that may be applied by any quality control laboratory. Chromatographic separation was performed using a Vertical RP-18 column programmed to run a gradient elution with sodium acetate buffer and acetonitrile. Flow rate was 1.2 mL min−1 for a total run time of 15 min. Ultraviolet detection was set at 264 nm and the use of a photodiode array detector in scan mode allowed selectivity confirmation by peak purity evaluation. The analyte peak was found to be adequately separated from degradation products generated during forced degradation studies. Thus, the proposed method was found to accurately indicate stability and was sufficient for routine quantitative analysis of fosamprenavir in coated tablets without interference from major degradation products and excipients.

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