Oxidative stress in autosomal dominant polycystic kidney disease: player and/or early predictor for disease progression?

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 or PKD2 genes, is the most common hereditary renal disease. Renal manifestations of ADPKD are gradual cyst development and kidney enlargement ultimately leading to end-stage renal disease. ADPKD also causes extrarenal manifestations, including endothelial dysfunction and hypertension. Both of these complications are linked with reduced nitric oxide levels related to excessive oxidative stress (OS). OS, defined as disturbances in the prooxidant/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen and nitrogen free radicals. Next to endothelial dysfunction and hypertension, there is cumulative evidence that OS occurs in the early stages of ADPKD. In the current review, we aim to summarize the cardiovascular complications and the relevance of OS in ADPKD and, more specifically, in the early stages of the disease. First, we will briefly introduce the link between ADPKD and the early cardiovascular complications including hypertension. Secondly, we will describe the potential role of OS in the early stages of ADPKD and its possible importance beyond the chronic kidney disease (CKD) effect. Finally, we will discuss some pharmacological agents capable of reducing reactive oxygen species and OS, which might represent potential treatment targets for ADPKD

Recent Advances in Portable Analytical Electromigration Devices

This article presents an overview of recent advances in the field of portable capillary electrophoresis and microchip electrophoresis equipment during the period 2013–Mid 2015. Instrumental achievements in the separation as well as the detection part of the equipment are discussed. Several applications from a variety of fields are described

Quantitative mass spectrometry methods for pharmaceutical analysis

Quantitative pharmaceutical analysis is nowadays frequently executed using mass spectrometry. Electrospray ionization coupled to a (hybrid) triple quadrupole mass spectrometer is generally used in combination with solid-phase extraction and liquid chromatography. Furthermore, isotopically labelled standards are often used to correct for ion suppression. The challenges in producing sensitive but reliable quantitative data depend on the instrumentation, sample preparation and hyphenated techniques. In this contribution, different approaches to enhance the ionization efficiencies using modified source geometries and improved ion guidance are provided. Furthermore, possibilities to minimize, assess and correct for matrix interferences caused by co-eluting substances are described. With the focus on pharmaceuticals in the environment and bioanalysis, different separation techniques, trends in liquid chromatography and sample preparation methods to minimize matrix effects and increase sensitivity are discussed. Although highly sensitive methods are generally aimed for to provide automated multi-residue analysis, (less sensitive) miniaturized set-ups have a great potential due to their ability for in-field usage.This article is part of the themed issue 'Quantitative mass spectrometry'.status: publishe

High-Resolution MS and MSn Investigation of UV Oxidation Products of Phenazone-type Pharmaceuticals and Metabolites

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. The occurrence of phenazone-type analgesics, such as aminopyrine, metamizole, phenazone and propyphenazone, has been reported in the effluent of wastewater treatment plants in µg/L concentrations. The presence of the main metabolites of aminopyrine and metamizole—acetamido antipyrine and formyl aminoantipyrine—has even been detected in sub µg/L concentrations in surface water and water bodies used to produce drinking water. This points at their high persistence and the need for adequate removal strategies. The degradation of phenazone, propyphenazone, acetamido antipyrine and formyl aminoantipyrine by UV radiation was investigated under laboratory conditions. An elucidation approach based on high-resolution mass spectrometry resulted in the identification of 11 degradation products. A mechanism of ring opening via the oxidation of the N–N bond of the pyrazolone ring was observed as well as the more typical oxidation of carbon–carbon double bonds. Aside from the degradation products, the capacity of formyl aminoantipyrine to produce trimers and dimers was demonstrated. The dimers were shown to be persistent despite continuous UV radiation. The toxicity of the degradation products was assessed by quantitative structure–activity relationships. It was shown that when the carbon–carbon double bond is partially oxidized to an epoxy the toxicity towards fish and daphnid is increased with respect to the parent compound.status: publishe

Study of Abl1 tyrosine kinase inhibitors by liquid chromatography-electrospray ionization-mass spectrometry

A method to study Abl1 tyrosine kinase inhibitors (TKIs) by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was developed and validated. Chromatographic separation was achieved on a Symmetry(®) C-18 column using a gradient. The detection was performed by selected ion monitoring (SIM) mode via positive ESI interface. The limit of quantification (LOQ) was 40.8 nM for p-Abltide [product, KKGEAIpYAAPFA-NH2] and 26.7 nM for Abltide (substrate, KKGEAIYAAPFA-NH2). The residual plot of linearity calibration curve indicated a good fit with a linear model. Intra- and inter-day precision was less than 10% and accuracy was from -6.93% to +0.15%. Matrix effect was not significant in this method. The validated method was applied to an Abl1 TKIs study. Imatinib mesylate (IM) and dasatinib were used to evaluate this method and the IC50 values were 202.1 nM and 925.1 pM, respectively. Two natural products (-)- epigallocatechingallate (EGCG) and caffeic acid were tested with this model. The IC50 value of EGCG was found at 64.03 nM and caffeic acid showed fluctuant inhibitory activity from 26% to 55% in the concentration range from 1 nM to 1mM. The IC50 value of a dimethylpyrrole hydroxylbenzoic acid derivative (MPB) was 1.915 μM.status: publishe

Analysis of volatile organic compounds in fuel oil by headspace GC-MS

© 2018 Informa UK Limited, trading as Taylor & Francis Group. Fuel oils are mostly used in marine applications and in power plants. They are known to contain hazardous volatile organic compounds (VOCs) that are of health and environmental importance. Chlorinated compounds, phenolic compounds, styrenes, indene, dicyclopentadiene, dihydrodicyclopentadiene, cumene, benzene, toluene, ethylbenzene and xylenes are some of the VOCs that have found their way into fuel oil through various streams during bunkering operation. Chromatographic analysis of VOCs in the presence of complex matrices in fuel oil is one of the major challenges encountered when dealing with products of that nature. An analytical procedure using automated static headspace gas chromatography–mass spectrometry was developed for the analysis of these compounds in fuel oil. Styrene D8 and phenol D6 were used as internal standards for quantitation. Phenol D6 was used for the quantitation of phenolic compounds, while styrene D8 was used for the quantitation of other target analytes. The influence of headspace parameters on analyte response such as temperature, incubation time and sample amount were all investigated and optimised. Linear calibration curves were achieved for all components with determination coefficients R2 > 0.995. Repeatability, limit of detection, limit of quantitation and recovery were reported. The matrix effect in fuel oil was minimised by 1:1 dilution with mineral oil. This method was successfully applied to the analysis of commercial samples.status: publishe

Six months stability investigation of sufentanil and ropivacaine/levobupivacaine admixtures in plastic containers by LC-UV

The stability of sufentanil-ropivacaine and sufentanil-levobupivacaine solutions was evaluated during 6 months while stored at 4 °C. Containers for sufentanil-ropivacaine were syringe (made of polypropylene (PP)) and cassette (inside bag of polyvinylchloride) and for sufentanil-levobupivacaine syringe (PP) and infusion bag (inner layer of PP). A liquid chromatographic (LC) method was validated and allowed the measurement of the three analytes. Both solutions were found to be stable under the examined conditions with contents that remained close to 100 %.status: publishe

Thin-Layer Chromatography-Flame Ionization Detection

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