A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of phenolic polycyclic aromatic hydrocarbons (OH-PAH) in urine of non-smokers and smokers

Polycyclic aromatic hydrocarbons (PAH) are products of the incomplete combustion of organic materials and, therefore, occur ubiquitously in the environment and also in tobacco smoke. Since some PAH have been classified as carcinogens, it is important to have access to suitable analytical methods for biomarkers of exposure to this class of compounds. Past experience has shown that measuring a profile of PAH metabolites is more informative than metabolites of a single PAH. Assessment of environmental and smoking-related exposure levels requires analytical methods with high sensitivity and specificity. In addition, these methods should be fast enough to allow high throughput. With these pre-conditions in mind, we developed and validated a high-performance liquid chromatographic method with tandem mass spectrometric detection (LC-MS/MS) for the determination of phenolic metabolites of naphthalene, fluorene, phenanthrene and pyrene in urine of smokers and non-smokers. Sample work-up comprised enzymatic hydrolysis of urinary conjugates and solid-phase extraction on C18 cartridges. The method showed good specificity, sensitivity, and accuracy for the intended purpose and was also sufficiently rapid with a sample throughput of about 350 per week. Application to urine samples of 100 smokers and 50 non-smokers showed significant differences between both groups for all measured PAH metabolites, and strong correlations with markers of daily smoke exposure in smoker urine. Urinary levels were in good agreement with previously reported data using different methodologies. In conclusion, the developed LC-MS/MS method is suitable for the quantification of phenolic PAH metabolites of naphthalene, fluorene, phenanthrene, and pyrene in smoker and non-smoker urine.     

Book reviews

Communicated by Professor Zimmermann     

Theoretical and experimental analysis of the luminescence signal of singlet oxygen for different photosensitizers

After the generation by different photosensitizers, the direct detection of singlet oxygen is performed by measuring its luminescence at 1270 nm. Using an infrared sensitive photomultiplier, the complete rise and decay time of singlet oxygen luminescence is measured at different concentrations of a photosensitizer, quencher, or oxygen. This allows the extraction of important information about the photosensitized generation of singlet oxygen and its decay, in particular at different oxygen concentrations. Based on theoretical considerations all important relaxation rates and rate constants were determined for the triplet T(1) states of the photosensitizers and for singlet oxygen. In particular, depending on the oxygen or quencher concentration, the rise or the decay time of the luminescence signal exhibit different meanings regarding the lifetime of singlet oxygen or triplet T(1)-state. To compare with theory, singlet oxygen was generated by nine different photosensitizers dissolved in either H2O, D2O or EtOD. When using H2O as solvent, the decaying part of the luminescence signal is frequently not the lifetime of singlet oxygen, in particular at low oxygen concentration. Since cells show low oxygen concentrations, this must have an impact when looking at singlet oxygen detection in vitro or in vivo.     

Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters

Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin‐derived N‐Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto’s catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/cholecystokinin‐B receptor antagonist AG‐041R.     

Millifluidic as a versatile reactor to tune size and aspect ratio of large polymerized objects

The continuous production “on demand” of large polymerized objects is presented using a versatile, easy to implement and low cost “millifluidic” reactor. Over microfluidic devices, the present set-up offers two considerable advantages: (i) much larger particles are produced with a very good control of sizes and shapes and (ii) no lithography is required for its design. Considering the high modularity of this synthetic pathway, “tubular millifluidic” appears as a new concept of synthesizing particles with a strong control over final object sizes, monodispersity and aspect ratio. The possibility to reach a high scale production makes it a promising production tools for the industry.     

Training neural networks with noisy data as an ill-posed problem

This paper is devoted to the analysis of network approximation in the framework of approximation and regularization theory. It is shown that training neural networks and similar network approximation techniques are equivalent to least-squares collocation for a corresponding integral equation with mollified data.Results about convergence and convergence rates for exact data are derived based upon well-known convergence results about least-squares collocation. Finally, the stability properties with respect to errors in the data are examined and stability bounds are obtained, which yield rules for the choice of the number of network elements.     

Controlled production of hierarchically organized large emulsions and particles using assemblies on line of co-axial flow devices

We describe a continuous flow scheme to conceive and produce hierarchically organized large emulsions and particles with very good control over size, shape and internal structure. By assembling together elementary co-axial flow modules and integrating their corresponding functions, modular set-ups can be designed “on demand” to engineer complex architectures in characteristic sizes ranging from 50 μm up to a few millimeters. The high potentiality of this approach stems from the continuous production of drops and the ability to manipulate and functionalize each one independently “on line”. Its great versatility is limited only by the number of combinations possible using the modular toolbox and one's imagination. We illustrate this through the encapsulation of droplets or solid particles of various shapes, composition and size, in liquid or solidified drops as well as the formation of large organic or inorganic cylindrical particles.