European Pharma Oligonucleotide Consortium: A Move to Consolidate Oligonucleotide Knowledge and Share Experience Within the Community.

A consortium of seven pharma companies has been formed with the aim of sharing knowledge on and harmonizing approaches to oligonucleotide development. This letter aims to raise awareness of this new group and to set expectations for future publications.

Photochemical stability of 4'-azido-2'-deoxy-2'-methylcytidine hydrochloride: structural elucidation of major degradation products by LC-MS and NMR analysis.

The photochemical stability of (1'R,2'S,3'S,4'R)-4'-azido-2'-deoxy-2'-methylcytidine hydrochloride, a new anti-HCV agent, was investigated. Aqueous solutions and bulk drug powder of the drug candidate were exposed to UV-visible light, complying with ICH requirements. The nucleoside analog decomposed via loss of nitrogen to yield products derived from a highly reactive azide intermediate. Major photolysis products were identified by LC-MS and NMR analysis, revealing three main photodegradation pathways. The first one led to the formation of a ring-expanded imidate ester. The other degradation pathways involved exocyclic or endocyclic bond cleavage with imine or imino lactone formation. The latter were prone to rapid hydrolysis, eventually resulting in the release of cytosine, 2-methyl malonaldehyde and (E)-cytosyl-2-methylpropenal.

Priority volatile organic compounds in surface waters of the southern North Sea.

The occurrence of 25 volatile organic compounds (VOCs) was studied from April 1998 to October 2000 in the southern North Sea. Target VOCs were selected from lists of priority pollutants for the marine environment and included, e.g., chlorinated short-chain hydrocarbons (CHCs), monocyclic aromatic hydrocarbons (MAHs), and chlorinated monocyclic aromatic hydrocarbons (CMAHs). Water samples were taken from the Channel, the Belgian Continental Shelf, the mouth of the Scheldt estuary and the Southern Bight, and were analysed by purge-and-trap and high-resolution gas chromatography-mass spectrometry. All data were produced by analyses deemed 'in control' by a rigorous quality assurance/quality control program provided by QUASIMEME (Quality Assurance of Information for Marine Environmental Monitoring in Europe). Chloroform and trichloroethene were commonly detected at concentrations up to 1900 and 270 ng l(-1), respectively. The other CHCs were generally found below 5 ng l(-1), and rarely exceeded 10 ng l(-1). Concentrations of MAHs were at least one order of magnitude higher than those of the CHCs. The higher levels were attributed to anthropogenic emissions from oil-related activities in coastal areas. CMAHs, except chlorobenzene and 1,4-dichlorobenzene, were hardly detected in North Sea waters. The levels of several CHCs and MAHs were shown to decrease compared to previous investigations in 1994-1995, probably as a result of on-going emission reduction efforts. The occurrence of 1,1,1-trichloroethane, for instance, was substantially reduced since the Montreal Protocol was implemented in 1995.

Spatial and temporal variability of priority volatile organic compounds in the Scheldt estuary.

The occurrence and spatial-temporal variability of 25 volatile organic compounds (VOCs) was studied from May 1998 to November 2000 in the Scheldt estuary. Target VOCs were selected from lists of priority pollutants to the North Sea, and included chlorinated short-chain hydrocarbons (CHCs), monocyclic aromatic hydrocarbons (MAHs) and chlorinated monocyclic aromatic hydrocarbons (CMAHs). Samples were taken between Vlissingen and Temse over a 95 km trajectory, and analysed by purge-and-trap and high resolution gas chromatography-mass spectrometry. Data were attended by analyses deemed 'in control' by a rigorous quality assurance/quality control program, as proposed by Quality Assurance of Information for Marine Environmental Monitoring in Europe (QUASIMEME). CHCs were among the most commonly found VOCs in the estuary, ranging from a few ng l(-1) to several microg l(-1). Most analytes were traceable to a single input source in the upper part of the estuary, which is densely populated and highly industrialized. By contrast, the occurrence of MAHs resulted from contributions of a wide spectrum of sources. The CMAHs were less abundant in the water column, and were mainly detected as chlorobenzene and 1,4-dichlorobenzene. Concentrations of several priority VOCs have markedly decreased since 1995 owing to emission reduction efforts within international frameworks for the protection of the North Sea.

State-of-the-art of gas chromatography-based methods for analysis of anthropogenic volatile organic compounds in estuarine waters, illustrated with the river Scheldt as an example.

This review focuses on a number of key procedural steps in the analysis of volatile organic compounds (VOCs) in estuarine waters. The most critical step, from an analytical point of view, is sample preparation. So far, only purge-and-trap and, to some extent, membrane inlet mass spectrometry have successfully been applied in estuarine monitoring of VOCs. The advantages and disadvantages of both techniques are discussed and novel developments are reviewed. Other key elements in VOC analysis and assessment include quality assurance (QA), quality control (QC) and statistical data analysis. This paper gives a brief overview of QA/QC measures of interest in the estuarine monitoring exercise, and provides guidelines for adequate statistical treatment of environmental data. Finally, field measurements of VOCs in estuarine waters are reviewed. Concentrations are reported, and distribution patterns, sources and time-trends are discussed. In addition to data, results of a 3-year monitoring survey (May 1998-November 2000) in the Scheldt estuary are presented.

Trace analysis of trichlorobenzenes in fish by microwave-assisted extraction and gas chromatography-electron-capture detection.

An analytical method consisting of extraction, clean-up, and analysis by gas chromatography-electron-capture detection (GC-ECD) was developed for the determination of trichlorobenzenes (TCBs) in fish samples. Two extraction methods, saponification and liquid-liquid extraction (S-LLE), and microwave-assisted extraction (MAE), were evaluated. In both cases, n-pentane was used as the extraction solvent. For S-LLE, the recoveries ranged from 66.6+/-9.1% for 1-bromo-4-chlorobenzene (4-BCB) to 93.5+/-4.9% for 1,2,4-trichlorobenzene (1,2,4-TCB). The recoveries were significantly lower, between 31.0+/-3.9% for 1,2,3-trichlorobenzene (1,2,3-TCB) and 52.3+/-3.0% for 1,3,5-trichlorobenzene (1,3,5-TCB), in the absence of fish. Proteins and glycerides of the fish tissue seemed to compete with TCBs for the base, and hence decreased their decomposition rate. In the case of MAE, the recoveries were highly dependent on the pressure applied during extraction. At 5 bar, much higher recoveries were obtained, from 66.7+/-15.6% for 4-BCB to 79.9+/-13.6% for 1,2,4-TCB, than at 1 bar. Sulfur formation was, however, observed at 5 bar, and interfered with the GC-ECD analysis of TCBs. Sulfur was adequately removed by copper powder treatment, which was shown not to affect the recovery of analytes. The recoveries of target analytes by S-LLE and MAE did not differ statistically (t-test, alpha = 0.01). Both methods were appropriate for the detection of TCBs at concentration levels typically observed in marine biota, i.e. approximately 1 ng/g. S-LLE was, however, more time consuming, and required larger volumes of high-purity organic solvents than MAE.

How to estimate moments and quantiles of environmental data sets with non-detected observations? A case study on volatile organic compounds in marine water samples.

Concentrations of 27 priority volatile organic compounds were measured in water samples of the North Sea and Scheldt estuary during a 3-year monitoring study. Despite the use of a sensitive analytical method, a number of data were censored. That is, some concentrations were below the decision limit or critical level defined by IUPAC. To characterize the observed measurement results, an attempt was made to identify an appropriate procedure to compute summary statistics for the censored data sets. Several parametric and robust parametric approaches based on the maximum likelihood principle and probability-plot regression method were evaluated for the estimation of the mean, standard deviation, median and interquartile range using three uncensored analytes (1,1,2-trichloroethane, tetrachloroethene and o-xylene) from the monitoring survey. Performance was assessed by artificially censoring the observed concentrations and estimating moments and quantiles at each censoring level. Results showed that methods with the least distributional assumptions, such as the robust bias-corrected restricted maximum likelihood method, perform best for estimating the mean and standard deviation, while both parametric and robust parametric techniques can be used for quantiles. Hence, summary statistics could be estimated with little bias (5-10%) up to 80% of censoring for the data sets employed in this study.