A Validated Stability-Indicating LC Method for Orbifloxacin in the Presence of Degradation Products

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Photoelectrocatalytic degradation of Remazol Brilliant Orange 3R on titanium dioxide thin-film electrodes

Degradation of reactive dye Remazol Brilliant Orange 3R (RBO) has been performed using photoeletrocatalysis. A biased potential is applied across a titanium dioxide thin-film photoelectrode illuminated by UV light. It is suggested that charges photogenerated at the electrode surface give rise to chlorine generation and powerful oxidants (OH) that causes the dye solution to decolorize. Rate constants calculated from color decay versus time reveal a first-order reaction up to 5.0×10-5 mol l-1 in dye concentration. The best experimental conditions were found to be pH 6.0 and 1.0 mol l-1 NaCl when the photoelectrode was biased at +1V (versus SCE). Almost complete mineralization of the dye content (70% TOC reduction) was achieved in a 3-h period using these conditions. Effects of other electrolytes, dye concentration and applied potentials also have been investigated and are discussed. © 2003 Elsevier Science B.V. All rights reserved.

Photodegradation of sparfloxacin and isolation of its degradation products by preparative HPLC

Sparfloxacin, a third generation fluoroquinolone derivative, is a potent antibacterial agent active against a wide range of Gram-positive and Gram-negative organisms including Streptococcus pneuinoniae, Staphylococcus aureus, methicillin resistant S. aureus, Legionella spp., Mycoplasina spp., Chlamydia spp. and Mycobacterium spp. A drawback of fluoroquinolones is their photoreactivity. Sparfloxacin has been studied in terms of therapeutic activities. However, there are few published of analytical methods being applied to sparfloxacin. The aim in this study was to determine the photodegradation products of sparfloxacin, when submitted to UV light, and to characterize two of these products, designated SPAX-PDP1 and SPAX-PDP2. An accelerated study of stability in methanol solution was carried out by exposing a solution of sparfloxacin to UV light (peak wavelength 290 nm) for 36 hours at room temperature. The products were analyzed by NMR spectrophotometry, IR spectrometry and mass spectrophotometry. The results suggest that the products isolated here could be used to estimate the degradation of sparfloxacin in a stability study. However, the low activity exhibited by UV-irradiated sparfloxacin is a source of concern that demands further investigation of the mechanism of its photodegradation mechanism.

Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery

The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery. © 2006 Bentham Science Publishers Ltd.

The effect of pH on horseradish peroxidase-catalyzed oxidation of melatonin: Production of N1-acetyl-N2-formyl-5- methoxykynuramine versus radical-mediated degradation

There is a growing body of evidence that melatonin and its oxidation product, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), have anti-inflammatory properties. From a nutritional point of view, the discovery of melatonin in plant tissues emphasizes the importance of its relationship with plant peroxidases. Here we found that the pH of the reaction mixture has a profound influence in the reaction rate and products distribution when melatonin is oxidized by the plant enzyme horseradish peroxidase. At pH 5.5, 1 mm of melatonin was almost completely oxidized within 2 min, whereas only about 3% was consumed at pH 7.4. However, the relative yield of AFMK was higher in physiological pH. Radical-mediated oxidation products, including 2-hydroxymelatonin, a dimer of 2-hydroxymelatonin and O-demethylated dimer of melatonin account for the fast consumption of melatonin at pH 5.5. The higher production of AFMK at pH 7.4 was explained by the involvement of compound III of peroxidases as evidenced by spectral studies. On the other hand, the fast oxidative degradation at pH 5.5 was explained by the classic peroxidase cycle. © 2007 The Authors.

Effect of phosphoric acid on the degradation of human dentin matrix

This study determined if dentin proteases are denatured by phosphoric acid (PA) used in etch-and-rinse dentin adhesives. Dentin beams were completely demineralized with EDTA for 30 days. We acid-etched experimental groups by exposing the demineralized dentin beams to 1, 10, or 37 mass% PA for 15 sec or 15 min. Control beams were not exposed to PA but were incubated in simulated body fluid for 3 days to assay their total endogenous telopeptidase activity, by their ability to solubilize C-terminal crosslinked telopeptides ICTP and CTX from insoluble dentin collagen. Control beams released 6.1 ± 0.8 ng ICTP and 0.6 ± 0.1 ng CTX/mg dry-wt/3 days. Positive control beams pre-incubated in p-aminophenylmercuric acetate, a compound known to activate proMMPs, released about the same amount of ICTP peptides, but released significantly less CTX. Beams immersed in 1, 10, or 37 mass% PA for 15 sec or 15 min released amounts of ICTP and CTX similar to that released by the controls (p > 0.05). Beams incubated in galardin, an MMP inhibitor, or E-64, a cathepsin inhibitor, blocked most of the release of ICTP and CTX, respectively. It is concluded that PA does not denature endogenous MMP and cathepsin activities of dentin matrices. © 2013 International & American Associations for Dental Research.

2,4-Dichlorophenoxyacetic acid (2,4-D) degradation promoted by nanoparticulate zerovalent iron (nZVI) in aerobic suspensions

Reactive species generated by Fe0 oxidation promoted by O2 (catalyzed or not by ligands) are able to degrade contaminant compounds like the herbicide 2,4-dichlorophenoxyacetic acid. The degradation of 2,4-D was influenced by the concentrations of zero valent iron (ZVI) and different ligands, as well as by pH. In the absence of ligands, the highest 2,4-D degradation rate was obtained at pH 3, while the highest percentage degradation (50%) was achieved at pH 5 after 120 min of reaction. Among the ligands studied (DTPA, EDTA, glycine, oxalate, and citrate), only ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) significantly enhanced oxidation of 2,4-D. This increase in oxidation was observed at all pH values tested (including neutral to alkaline conditions), indicating the feasibility of the technique for treatment of contaminated water. In the presence of EDTA, the oxidation rate was greater at pH 3 than at pH 5 or 7. Increasing the EDTA concentration increased the rate and percentage of 2,4-D degradation, however increasing the Fe0 concentration resulted in the opposite behavior. It was found that degradation of EDTA and 2,4-D occurred simultaneously, and that the new methodology avoided any 2,4-D removal by adsorption/coprecipitation. © 2013 Elsevier Ltd.

Stability-indicating thin-layer chromatographic method for determination of darunavir in complex darunavir-beta-cyclodextrin in the presence of its degradation products

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

On-line monitoring of electrochemical degradation of paracetamol through a biomimetic sensor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Thermal stability and thermal decomposition of the antihypertensive drug amlodipine besylate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stability study and degradation kinetics of ceftazidime in pharmaceutical preparations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation and degradation chemistry of orbifloxacin using LC-MS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Crystal structure of isotibolone: a major degradation product of tibolone

Isotibolone is frequently found as an impurity in tibolone, a drug used for hormone reposition of post-menopause women, due to some inadequate tibolone synthesis or as a result of degradation during drug storage. The presence of isotibolone impurities should be detected and quantified in active pharmaceutical ingredient products of tibolone before its use in the manufacturing of medicaments. The X-ray powder diffraction technique offers the possibility of quantifying isotibolone amounts at different stages of drug production and storage, from the chemical synthesis to the final formulation. In the course of a study involving the quantitative analysis of isotibolone by X-ray powder diffraction, the authors determined the structure of the title compound using a recently developed approach (A. Gomez and S. Kycia, J. Appl. Crystallogr. 2011, 44, 708-713). The structure is monoclinic, space group P2(1) (4), with unit cell parameters a = 6.80704(7) angstrom, b = 20.73858(18) angstrom, c = 6.44900(6) angstrom, beta = 76.4302(5)degrees, V = 884.980(15) angstrom(3) and two molecules per unit cell (Z = 2). The molecules are hydrogen bonded in the ab plane forming layers that are held together in the crystal by van der Waals interactions along the c-axis.

Osteoinductive implants: the mise-en-scène for drug-bearing biomimetic coatings

In orthopaedic and dental implantology, novel tools and techniques are being sought to improve the regeneration of bone tissue. Numerous attempts have been made to enhance the osteoconductivity of titanium prostheses, including modifications in their surface properties and coating with layers of calcium phosphate. The technique whereby such layers are produced has recently undergone a revolutionary change, which has had profound consequences for their potential to serve as drug-carrier systems. Hitherto, calcium phosphate layers were deposited upon the surfaces of metal implants under highly unphysiological physical conditions, which precluded the incorporation of proteinaceous osteoinductive drugs. These agents could only be adsorbed, superficially, upon preformed layers. Such superficially adsorbed molecules are released too rapidly within a biological milieu to be effective in their osteoinductive capacity. Now, it is possible to deposit calcium phosphate layers under physiological conditions of temperature and pH by the so-called biomimetic process, during which bioactive agents can be coprecipitated. Since these molecules are integrated into the inorganic latticework, they are released gradually in vivo as the layer undergoes degradation. This feature enhances the capacity of these coatings to act as a carrier system for osteogenic agents.

Evolutionarily conserved role of calcineurin in phosphodegron-dependent degradation of phosphodiesterase 4D.

Calcineurin is a widely expressed and highly conserved Ser/Thr phosphatase. Calcineurin is inhibited by the immunosuppressant drug cyclosporine A (CsA) or tacrolimus (FK506). The critical role of CsA/FK506 as an immunosuppressant following transplantation surgery provides a strong incentive to understand the phosphatase calcineurin. Here we uncover a novel regulatory pathway for cyclic AMP (cAMP) signaling by the phosphatase calcineurin which is also evolutionarily conserved in Caenorhabditis elegans. We found that calcineurin binds directly to and inhibits the proteosomal degradation of cAMP-hydrolyzing phosphodiesterase 4D (PDE4D). We show that ubiquitin conjugation and proteosomal degradation of PDE4D are controlled by a cullin 1-containing E(3) ubiquitin ligase complex upon dual phosphorylation by casein kinase 1 (CK1) and glycogen synthase kinase 3beta (GSK3beta) in a phosphodegron motif. Our findings identify a novel signaling process governing G-protein-coupled cAMP signal transduction-opposing actions of the phosphatase calcineurin and the CK1/GSK3beta protein kinases on the phosphodegron-dependent degradation of PDE4D. This novel signaling system also provides unique functional insights into the complications elicited by CsA in transplant patients.