scholarly journals First Total Synthesis of 3a-hydroxy-1,1-dimethyl-5-((N-methylsulfamoyl)methyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-1-ium 2,2,2-trifluoroacetate by Mimicking the Oxidative Degradation Pathway of Sumatriptan

2021 ◽  
pp. 100173
Author(s):  
Pradip K. Sasmal ◽  
Ganesh Ramachandran ◽  
Ying Zhang ◽  
Zhong Liu
2005 ◽  
Vol 46 (20) ◽  
pp. 3533-3536 ◽  
Author(s):  
Min Li ◽  
Beth Conrad ◽  
Russell G. Maus ◽  
Steven M. Pitzenberger ◽  
Raju Subramanian ◽  
...  

2019 ◽  
Vol 17 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Fawzia A. Ibrahim ◽  
Amina M. El-Brashy ◽  
Mohamed I. El-Awady ◽  
Nora. A. Abdallah

AbstractThe native fluorescence of sotalol hydrochloride (SOT) was used as a basis for establishing a new method of analysis for SOT in tablets and spiked human plasma. The fluorescence of SOT in water was measured at 310 nm when excited at 235 nm. The detection limit (LOD) was 0.37 ng/mL and the quantification limit (LOQ) was 1.08 ng/mL. The proposed method offers high sensitivity which permits determination of SOT, even if present in a very small amount, in human plasma. The obtained results were successfully compared to that of a reference pharmacopeial method and statistical analysis proved a good agreement between the results of both methods. Further investigation of the SOT stability upon exposure to various stress conditions, such as acidic, alkaline, oxidative and photolytic degradation conditions was also performed. The kinetics of acidic, alkaline and oxidative degradation of the drug showed a pseudo first order degradation reaction. A proposal of the degradation pathway was suggested and confirmed by developing a thin layer chromatographic method used for separation of SOT and its acidic and alkaline degradation products.


2021 ◽  
Vol 3 (6) ◽  
Author(s):  
Chandrakant Sojitra ◽  
Chintan Dholakia ◽  
Padmaja Sudhakar ◽  
Kumar K. Singh ◽  
Sameer Agarwal

AbstractForced degradation study is a systemic characterization of degradation products of active pharmaceutical ingredient (API) at conditions which posses more harsh environment that accelerates degradation of API. Forced degradation and stability studies would be useful in selection of proper, packaging material and storage conditions of the API. These are also useful to demonstrate degradation pathways and degradation products of the API and further characterisation of the degradation products using mass spectrometry. TGR5 is a G protein-coupled receptor, activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The potent and orally bioavailable TGR5 agonist, ZY12201, shows activation of TGR5 which increase secretion of GLP-1 and help in lowering blood glucose level in animal models. Hence it is necessary to establish and study degradation pathway and stability of API for better handling and regulatory approval. Force degradation studies of ZY12201 have shown presence of one oxidative impurity during oxidative degradation in HPLC analysis. The oxidized product is further characterized by LC–MS to elucidate structure of impurity and characterize its degradation pathway.


2020 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Ebtihal Samir ◽  
Mamdouh Mamdouh ◽  
Sayed M Derayea

1984 ◽  
Vol 177 (1-2) ◽  
pp. 293-297 ◽  
Author(s):  
Tetsuhiko Kobayashi ◽  
Hiroshi Yoneyama ◽  
Hideo Tamura

2020 ◽  
Vol 16 ◽  
Author(s):  
Ola Mohamed EL-Houssini ◽  
Nagwan Hamdi Zawilla ◽  
Mohammad Abdul-Azim Mohammad

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.


2019 ◽  
Vol 202 (3) ◽  
Author(s):  
Ulrike Johnsen ◽  
Jan-Moritz Sutter ◽  
Andreas Reinhardt ◽  
Andreas Pickl ◽  
Rui Wang ◽  
...  

ABSTRACT The Haloarcula species H. marismortui and H. hispanica were found to grow on d-ribose, d-xylose, and l-arabinose. Here, we report the discovery of a novel promiscuous oxidative pathway of pentose degradation based on genome analysis, identification and characterization of enzymes, transcriptional analysis, and growth experiments with knockout mutants. Together, the data indicate that in Haloarcula spp., d-ribose, d-xylose, and l-arabinose were degraded to α-ketoglutarate involving the following enzymes: (i) a promiscuous pentose dehydrogenase that catalyzed the oxidation of d-ribose, d-xylose, and l-arabinose; (ii) a promiscuous pentonolactonase that was involved in the hydrolysis of ribonolactone, xylonolactone, and arabinolactone; (iii) a highly specific dehydratase, ribonate dehydratase, which catalyzed the dehydration of ribonate, and a second enzyme, a promiscuous xylonate/gluconate dehydratase, which was involved in the conversion of xylonate, arabinonate, and gluconate. Phylogenetic analysis indicated that the highly specific ribonate dehydratase constitutes a novel sugar acid dehydratase family within the enolase superfamily; and (iv) finally, 2-keto-3-deoxypentanonate dehydratase and α-ketoglutarate semialdehyde dehydrogenase catalyzed the conversion of 2-keto-3-deoxypentanonate to α-ketoglutarate via α-ketoglutarate semialdehyde. We conclude that the expanded substrate specificities of the pentose dehydrogenase and pentonolactonase toward d-ribose and ribonolactone, respectively, and the presence of a highly specific ribonate dehydratase are prerequisites of the oxidative degradation of d-ribose in Haloarcula spp. This is the first characterization of an oxidative degradation pathway of d-ribose to α-ketoglutarate in archaea. IMPORTANCE The utilization and degradation of d-ribose in archaea, the third domain of life, have not been analyzed so far. We show that Haloarcula species utilize d-ribose, which is degraded to α-ketoglutarate via a novel oxidative pathway. Evidence is presented that the oxidative degradation of d-ribose involves novel promiscuous enzymes, pentose dehydrogenase and pentonolactonase, and a novel sugar acid dehydratase highly specific for ribonate. This is the first report of an oxidative degradation pathway of d-ribose in archaea, which differs from the canonical nonoxidative pathway of d-ribose degradation reported for most bacteria. The data contribute to our understanding of the unusual sugar degradation pathways and enzymes in archaea.


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