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Your search keyword '"Drug degradation"' showing total 4 results
Start Over Descriptor "Drug degradation" Journal journal of pharmaceutical and biomedical analysis
4 results on '"Drug degradation"'

1. Potential of capillary electrophoresis for the monitoring of the stability of placental alkaline phosphatase

Author

M. Wijngaard, Govert W. Somsen, Henderik W. Frijlink, Wouter L. J. Hinrichs, G.J. de Jong, H.J.C. Eriksson, Pharmaceutical Technology and Biopharmacy, Nanotechnology and Biophysics in Medicine (NANOBIOMED), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), BioAnalytical Chemistry, and AIMMS

Subjects
temperature sensitivity, Hot Temperature, Placenta, Clinical Biochemistry, enzymatic activity, Pharmaceutical Science, Analytical Chemistry, chemistry.chemical_compound, Drug Discovery, Enzyme Stability, Protein stability, Spectroscopy, chemistry.chemical_classification, analytic method, biology, inulin, accuracy, pH, article, Hydrogen-Ion Concentration, Therapeutic protein, enzyme activity, Biochemistry, protein stability, priority journal, capillary zone electrophoresis, Alkaline phosphatase, room temperature, alkaline phosphatase, Phosphoric monoester hydrolases, Inulin, capillary electrophoresis, Capillary electrophoresis, drug activity, drug degradation, therapeutic protein, drug stability, Chromatography, Enzymatic activity, Electrophoresis, Capillary, Enzyme assay, Placental alkaline phosphatase, Enzyme, chemistry, freeze drying, biology.protein, Degradation (geology), alkaline phosphatase placenta isoenzyme
Abstract

Alkaline phosphatase (AP) is a potential therapeutic agent in the treatment of sepsis. In this paper the potential of capillary zone electrophoresis (CZE) for the monitoring of the degradation of placental alkaline phosphatase (PLAP) was investigated. To induce degradation PLAP samples were exposed to high temperatures, low and high pH and freeze-drying. The samples were then analyzed by CZE and enzymatic activity assay. Upon exposure to temperatures above 65 degreesC, PLAP lost its activity exponentially over time, while CZE revealed both a linear decrease of the area of the main peak and a rise of degradation products. At acidic pH the enzyme appeared to lose its activity. CZE revealed a decrease of the area of the main peak, but no degradation products could be detected. At pH 12 the enzymatic activity and the area of the main peak both decreased linearly over time and, in addition, formation of degradation products could be detected by CZE. Activity and CZE profile of PLAP remained unchanged upon freeze-drying in the presence of inulin. Prolonged storage of freeze-dried samples at room temperature caused a slight decrease of enzymatic activity, while the potential formation of oligomers was revealed by CZE analysis. The examples in this study show that, in combination with activity assays, CZE can provide useful complementary information, especially on the status of the protein and the presence of degradation products. (C) 2003 Elsevier Science B.V. All rights reserved.

Published
2003
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2. Feasibility of rapidly assessing reactive impurities mediated excipient incompatibility using a new method: A case study of famotidine-PEG system.

Author

Saraf I, Modhave D, Kushwah V, Neshchadin D, Gescheidt G, Trausinger G, Melchior P, Magnes C, and Paudel A

Subjects
Chemistry, Pharmaceutical methods, Chromatography, Liquid methods, Feasibility Studies, Oxidative Stress, Oxygen chemistry, Temperature, Drug Incompatibility, Excipients chemistry, Famotidine chemistry, Polyethylene Glycols chemistry
Abstract

The present work demonstrates the utility of temperature controlled set up with pressurized headspace oxygen as an approach to effectively reduce the time required for solid-state drug-excipient compatibility study. To illustrate the utility, the incompatibility of polyethylene glycol (PEG) and polyethylene oxide (PEO) with Famotidine (Fam) was shown. Owing to thermal and oxidative stress, polyethylene ether moieties of PEG generated reactive impurities, resulting in the degradation of Fam. The chemical degradation was evaluated via liquid chromatography. Around 20% of degradation was observed in the pressurized oxygen set up, whereas, no degradation was found in the absence of oxidative stress. On increasing the excipient fraction, the Fam degradation increased proportionally. Formation of aldehydes and free radicals from excipients were proposed as the precursors for Fam degradation. The generation of aldehydes and free radicals was confirmed by infrared and Electron Spin Resonance (ESR) spectroscopic analysis, respectively. Overall, the present study demonstrated the utility of pressurized oxygen set up as a rapid and routine tool for studying drug-excipient incompatibility at temperatures relevant drug-product manufacture., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2020
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3. Implementation of design of experiments for optimization of forced degradation conditions and development of a stability-indicating method for furosemide

Author

Bhupinder Singh, Moolchand Kurmi, Sanjay Kumar, and Saranjit Singh

Subjects
Chromatography, Time Factors, Chemistry, Hold time, business.industry, Design of experiments, Hydrolysis, Clinical Biochemistry, Pharmaceutical Science, Drug degradation, Factorial experiment, Hydrogen-Ion Concentration, Analytical Chemistry, Volumetric flow rate, Drug Stability, Furosemide, Drug Discovery, Forced degradation, Stability indicating, Degradation (geology), Process engineering, business, Oxidation-Reduction, Spectroscopy, Chromatography, High Pressure Liquid
Abstract

The study involved optimization of forced degradation conditions and development of a stability-indicating method (SIM) for furosemide employing the design of experiment (DoE) concept. The optimization of forced degradation conditions, especially hydrolytic and oxidative, was done by application of 2(n) full factorial designs, which helped to obtain the targeted 20-30% drug degradation and also enriched levels of degradation products (DPs). For the selective separation of the drug and its DPs for the development of SIM, DoE was applied in three different stages, i.e., primary parameter selection, secondary parameter screening and method optimization. For these three, IV-optimal, Taguchi orthogonal array and face-centred central composite designs were employed, respectively. The organic modifier, buffer pH, gradient time and initial hold time were selected as primary parameters. Initial and final organic modifier percentage, and flow rate came out as critical parameters during secondary parameter screening, which were further evaluated during method optimization. Based on DoE results, an optimized method was obtained wherein a total of twelve DPs were separated successfully. The study also exposed the degradation behaviour of the drug in different forced degradation conditions.

Published
2013

4. Photodegradation of aqueous argatroban investigated by LC/MS n : Photoproducts, transformation processes and potential implications.

Author

Secrétan PH, Karoui M, Bernard M, Ghermani N, Safta F, Yagoubi N, and Do B

Subjects
Arginine analogs & derivatives, Chromatography, Reverse-Phase methods, Mass Spectrometry methods, Sulfonamides, Photolysis, Pipecolic Acids analysis
Abstract

Argatroban (ARGA), used as intravenous anticoagulant drug, has been reported to photodegrade under light exposure, requiring specific precautions at handling, storage and administration. Thus, for the first time, aqueous ARGA photodegradation under aerobic conditions has been described in terms of photoproducts, phototransformation processes and potential implications. ARGA significant photoproducts were successfully separated and characterized by gradient reversed-phase liquid chromatography coupled with high-resolution multistage mass spectrometry (LC/HR-MS n ). Hitherto still not available in literature, ARGA in-depth fragmentation study was conducted so as to thoroughly sort out the main mechanisms specific to the molecule and therefore, to propose a fragmentation pattern relevant to the identification of ARGA related substances. Thereafter, in view of the structural characteristics of the photoproducts formed, ARGA photodegradation pathways could be worked out, showing that whether by direct photolysis or through photosensitization, the methyltetrahydroquinoline nitrogen and that of guanidine group would be mainly involved in photolysis initiation reactions, through one-electron oxidation along with proton loss. Desulfonation, cyclisation affording compounds of diazinane type, and/or rearrangements with transfer of the methyltetrahydroquinoline group toward the guanidine function were observed accordingly. Having a good insight into ARGA photodegradation pathways allows for consistent measures in view of mitigating or avoiding the drug decay and the related potential effects., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2016
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