The immunologic detection and characterization of cartilage proteoglycan degradation products in synovial fluids of patients with arthritis

We have examined the catabolism of the proteoglycans aggrecan, decorin and biglycan in fresh tendon samples and in explant cultures of tissue from the tensional and compressed regions of young and mature bovine tendons. A panel of well-characterized antibodies that recognize glycosaminoglycan or protein (linear or neoepitope) sequences was used to detect proteoglycans and proteoglycan degradation products that were both retained within the tissue and released into the culture medium. In addition, a reverse-transcriptase-mediated PCR analysis was used to examine the mRNA expression patterns of tendon proteoglycans and aggrecanases. The results of this study indicate a major role for aggrecanase(s) in the catabolism of aggrecan in bovine tendon. The study also provides a characterization of glycosaminoglycan epitopes associated with the proteoglycans of tendon, illustrating age-related changes in the isomers of chondroitin sulphate disaccharides that remain attached to the core protein glycosaminoglycan linkage region after digestion with chondroitinase ABC. Evidence for a rapid turnover of the small proteoglycans decorin and biglycan was also observed, indicating additional molecular pathways that might compromise the integrity of the collagen matrix and potentially contribute to tendon dysfunction after injury and during disease.

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Characterization of dissolved material during the initial phase of softwood kraft pulping

TAPPI Journal ◽

10.32964/tj12.1.37 ◽

2013 ◽

Vol 12 (1) ◽

pp. 37-43 ◽

Cited By ~ 1

Author(s):

HANNU PAKKANEN ◽

TEEMU PALOHEIMO ◽

RAIMO ALÉN

Keyword(s):

Mass Transfer ◽

Molecular Mass ◽

Initial Phase ◽

Degradation Products ◽

Kraft Pulping ◽

Reaction Products ◽

Cooking Temperature ◽

Molecular Masses ◽

Aliphatic Carboxylic Acids

The influence of various cooking parameters, such as effective alkali, cooking temperature, and cooking time on the formation of high molecular mass lignin-derived and low molecular mass carbohydrates-derived (aliphatic carboxylic acids) degradation products, mainly during the initial phase of softwood kraft pulping was studied. In addition, the mass transfer of all of these degradation products was clarified based on their concentrations in the cooking liquor inside and outside of the chips. The results indicated that the degradation of the major hemicellulose component, galactoglucomannan, typically was dependent on temperature, and the maximum degradation amount was about 60%. In addition, about 60 min at 284°F (140°C) was needed for leveling off the concentrations of the characteristic reaction products (3,4-dideoxy-pentonic and glucoisosaccharinic acids) between these cooking liquors. Compared with low molecular mass aliphatic acids, the mass transfer of soluble lignin fragments with much higher molecular masses was clearly slower.

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Synthesis and Characterization of Potential and Degraded Impurities of Regadenoson

Current Pharmaceutical Analysis ◽

10.2174/1573412915666190819095255 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1130-1139

Author(s):

Singaram Sathiyanarayanan ◽

Chidambaram Subramanian Venkatesan ◽

Senthamaraikannan Kabilan

Keyword(s):

Mass Spectra ◽

Degradation Products ◽

Hplc Method ◽

Forced Degradation ◽

Spectroscopic Techniques ◽

A2a Adenosine Receptor ◽

Degradation Study ◽

Related Substances ◽

Adenosine Receptor Agonist

Background: Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator and commonly used as a pharmacologic cardiac stressing agents. Methods: HPLC method was used for the analysis of related substances. The degraded impurities during the process were isolated and characterized by IR, Mass and NMR spectral analysis. Results: Forced degradation study of regadenoson under conditions of hydrolysis (neutral, acidic and alkaline) and oxidations suggested in the ICH Q1A(R2) was accomplished. The drug showed significant degradation under all the above conditions. On the whole, five novel degradation products were found under diverse conditions along with process related impurities which were not reported earlier. Conclusion: All the degradation products were well characterized by using advanced spectroscopic techniques like IR, 1H NMR, 13C NMR and Mass spectra. The identification of these impurities will be productive for the quality control during the production and stability behavior of the regadenoson drug substance.

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Characterization of stress degradation products of nintedanib by UPLC, UHPLC-Q-TOF/MS/MS and NMR: evidence of a degradation product with a structure alert for mutagenicity

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2021.114037 ◽

2021 ◽

pp. 114037

Author(s):

Vivek Dhiman ◽

Ankit Balhara ◽

Saranjit Singh ◽

Shristy Tiwari ◽

Samanthula Gananadhamu ◽

...

Keyword(s):

Degradation Product ◽

Degradation Products ◽

Stress Degradation ◽

Tof Ms

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

Journal of AOAC International ◽

10.5740/jaoacint.16-0218 ◽

2017 ◽

Vol 100 (4) ◽

pp. 1029-1037 ◽

Cited By ~ 1

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.

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