Trace analysis of fluoxetine and its metabolite norfluoxetine. Part I: development of a chiral liquid chromatography-tandem mass spectrometry method for wastewater samples

An enantioselective method for the determination of fluoxetine (a selective serotonin reuptake inhibitor) and its pharmacologically active metabolite norfluoxetine has been developed for raw and treated wastewater samples. The stable isotope-labeled fluoxetine and norfluoxetine were used in an extended way for extraction recovery calculations at trace level concentrations in wastewater. Wastewater samples were enriched by solid phase extraction (SPE) with Evolute CX-50 extraction cartridges. The obtained extraction recoveries ranged between 65 and 82% in raw and treated wastewater at a trace level concentration of 50 pM (15-16 ng L⁻¹). The target compounds were identified by the use of chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring (SRM) mode. The enantiomers were successfully resolved on a chiral α₁-acid glycoprotein column (chiral AGP) with acetonitrile and 10 mM ammonium acetate buffer at pH 4.4 (3/97, v/v) as the mobile phase. The effects of pH, amount of organic modifier and buffer concentration in the mobile phase were investigated on the enantiomeric resolution (R_s) of the target compounds. Enantiomeric R_s-values above 2.0 (1.03 RSD%, n = 3) were achieved for the enantiomers of fluoxetine and norfluoxetine in all mobile phases investigated. The method was validated by assessing parameters such as cross-contamination and carryover during SPE and during LC analysis. Cross-talk effects were examined during the detection of the analytes in SRM mode. In addition, the isotopic purity of fluoxetine-d₅ and norfluoxetine-d₅ were assessed to exclude the possibility of self-contamination. The interassay precision of the chromatographic separation was excellent, with relative standard deviations (RSD) equal to or lower than 0.56 and 0.81% in raw and treated wastewaters, respectively. The method detection and quantification limits (respectively, MDL and MQL) were determined by the use of fluoxetine-d₅ and norfluoxetine-d₅. The MQL for the single enantiomers ranged from 12 to 14 pM (3.6-4.3 ng L⁻¹) in raw wastewater and from 3 to 4 pM (0.9-1 ng L⁻¹) in treated wastewater. The developed method has been employed for the quantification of (R)-fluoxetine, (S)-fluoxetine and the enantiomers of norfluoxetine in raw and treated wastewater samples to be presented in Part II of this study.     

Influence of boundary structure and near neighbor crystallographic orientation on the dynamic damage evolution during shock loading

The role of crystallographic orientation on damage evolution in ductile metals during shock loading has been investigated. By utilizing large-grained copper specimens, it has been shown that the development of intragranular damage, in the form of void growth and coalescence, is influenced by the grain orientation with respect to the applied load. Additionally, strain incompatibility and the inability to promote transmission or activation of secondary dislocation slip across a grain boundary, are proposed as the likely cause for intergranular failure. Finally, the free surface velocity profiles of each grain, specifically the decay of the oscillations after the pull-back, correlated well with the amount of damage measured within the respective grain.     

N-aminopyrroledione-hydrazonoketene-pyrazolium oxide-pyrazolone rearrangements and pyrazolone tautomerism

Flash vacuum thermolysis (FVT) of 1-(dimethylamino)pyrrole-2,3-diones 5 causes extrusion of CO with formation of transient hydrazonoketenes 7. The transient ketenes 7 are observable in the form of weak bands at 2130 (7a) or 2115 cm-1 (7b) in the Ar matrix IR spectra resulting from either FVT or photolysis of either 5 or 1,1-dimethylpyrazolium-5-oxides 8, and these absorptions are in excellent agreement with B3LYP/6-31G* frequency calculations. Under FVT conditions the ketenes 7 cyclize to pyrazolium oxides 8, which undergo 1,4-migration of a methyl group to yield 1,4-dimethyl-3-phenylpyrazole-5(4H)-one 9a and 1,4,4-trimethyl-3- phenylpyrazole-5(4H)-one 9b. All three tautomers of 9a have been characterized, viz. the CH form 9a (most stable form in the gas phase, the solid state and solvents of low polarity), the OH form 9a' (metastable solid at room temperature) and the NH form 9a" (stable in aprotic dipolar solvents). The isomeric 1,4-dimethyl-5-phenylpyrazole-3(2H)- one 12 tautomerizes to the 3-hydroxypyrazole 12'. The crystal structure of the hydrochloride 14 of 9a'/9a" is reported, representing the first structurally characterised example of a protonated 5-hydroxypyrazole.     

[1,2,3]Triazoloazine/(Diazomethyl)azine Valence Tautomers from 5-Azinyltetrazoles

[1,2,3]Triazoloazines are formed by thermolysis of 5-azinyltetrazoles in the gasphase or in solution. Thus, 5-(2-pyridyl)tetrazole ( 7 ) and 5-(2-pyrazinyl)tetrazole ( 11 ) yield [1,2,3]triazolo[1,5-a]pyridine ( 9 ) and [1,2,3]triazolo[1,5-a]pyrazine ( 13 ), respectively, at 400°/10^?3 - 10^?5 Torr. 5-(2-Phenyl-4-quinazolinyl)tetrazole ( 15 ) gives 5-phenyl[1,2,3]triazolo[1,5-c]quinazoline ( 17 ) in 75% yield by heating under reflux in mesitylene solution. 2-(Diazomethyl)pyridine ( 8 ), a valence tautomer of 9 , can be trapped by fumaronitrile, leading to 3-(2-pyridyl)-1, 2-cyclopropanedicarbonitrile ( 19 ). The [1,2,3]triazoloazines undergo base catalysed H/D-exchange in D₂O solution.     

Adsorption of toluene-soluble polymers at the toluene–water interface

The adsorption of several toluene-soluble polymers at the toluene–water interface has been investigated by using the duNouy ring method of measuring interfacial tension γT /W . Polystyrene and poly(ethylene-co-vinyl acetate) (11.1 mole-% vinyl acetate) have little affinity for this interface at 29°C, but poly(methyl methacrylate) (PMMA) (M?_n = 420,000) and ethyl cellulose (EC) (M?_n = 50,100; 49.1% ethoxyl) adsorb significantly at concentrations as low as 1.0 × 10^?4 g/100ml. A plot of interfacial tension lowering versus initial logarithm of initial bulk phase polymer concentration is linear from 1.0 × 10^?4 to 1.0 × 10^?1 g/100 ml for EC and 1.0 × 10^?4 to 1.0 × 10^?2 g/100 ml for PMMA. When the PMMA concentration increases to 1.15 × 10^?1 g/100 ml, its adsorption behavior changes markedly. Prolonged time effects occur and adsorption becomes dependent upon dissolved water content of the toluene prior to formation of the toluene/water interface. Such effects are not observed with the other solutions studied. Increasing temperatures have variable effects on values of γT /W for the polymer solutions studied. Experiments with various polymer mixtures indicate that the polymer lowering T /W the most is preferentially adsorbed at the toluene–water interface and rapidly displaces less strongly adsorbed polymers.     

Electronic transition CN laser

An electric discharge pumped CN laser oscillating on the A²Π-X²Σ system is reported. Peak power of 20 kW in a 150 nsec fwhm pulse is obtained using a simple longitudinal electric discharge in several mmHg of HCN. Oscillation occurs on the (0,1) and (0,2) bands at ? 1.42 and 2.0μm respectively.     

Leben und Wirken Kurt Gödels

Ohne ZusammenfassungLaudatio anläßlich des Festkolloquiums am Institut für Mathematik der Universität Wien zum Gedächtnis vonKurt Gödel am 28. 4. 1980.     

15N Labelling: Potassium azide,tetrazoles and imidazoles

A simplified high-yield preparation of end-labelled potassium azide from K¹⁵NO₃ is described. Treatment of 4-chloropyrimidines with K¹⁵NN₂ and subsequent gas-phase pyrolysis gives ring-labelled 1-cyanoimidazoles in 80–100% yields. The cyano-groups in the latter are easily removed by hydrolysis.     

Extensions of the Petal Method for Vehicle Routeing

The petal method for vehicle routeing imposes special structure on the form of a feasible route. In this paper we show that by extending the definition of a petal route, more general forms of vehicle route can be generated without invalidating the important underlying property that optimal petal solutions can be produced very easily. It will also be shown that the optimal generalized petal solution can be produced efficiently by multiple applications of a shortest path algorithm.