Marina Radišić

Determination of pesticides in surface and ground waters by liquid chromatography-electrospray-tandem mass spectrometry.

The sensitive multiresidual analytical method for simultaneous analysis of 14 most commonly used agricultural pesticides in Serbia was developed and optimized. The selected insecticides, fungicides and herbicides belong to seven chemical classes (organophosphates, neonicotinoids, carbamates, diacylhydrazines, benzimidazoles, triazines and phenylureas). The method was based on solid-phase extraction followed by liquid chromatography-tandem mass spectrometry. The following parameters that may affect the SPE procedure efficiency were optimized: the sorbent type in combination with different elution solvents, the sample pH and the sample volume. For each pesticide, MS(n) analysis was performed and distinctive ions and transitions were selected for identification and quantification, as well as for confirmation purposes. External matrix-matched calibration method was used to eliminate variable matrix effect and ensure precise quantification. Good recoveries (72-129%), and low limits of detection (0.4-5.5 ng L(-1)) and quantification (1.1-18.2 ng L(-1)) were achieved for all selected pesticides. The developed and optimized method was successfully applied in the analysis of several river waters, as well as ground waters in Serbia, influenced by agriculture. The most frequently detected pesticide was carbendazim. Dimethoate, carbofuran and propazine were also found in the investigated samples.

Monomer elution from nanohybrid and ormocer-based composites cured with different light sources

OBJECTIVES To study monomer elution from four resin-based composites (RBCs) cured with different light sources. METHODS Twenty-eight premolars were randomly allocated to four groups. Standardized cavities were prepared and restored with a nanohybrid (Filtek Supreme XT or Tetric EvoCeram), an ormocer (Admira) or a microhybrid RBC (Filtek Z250) which served as control. Buccal restorations were cured with a halogen and oral restorations with an LED light-curing unit. Elution of diurethane dimethacrylate (UDMA), Bisphenol A diglycidylether methacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) was analyzed using high-performance liquid chromatography (HPLC) 1h to 28 days post-immersion in 75% ethanol. Data were analyzed using multivariate and repeated measures analysis of variance (α = 0.05). RESULTS The greatest elution of UDMA and BisGMA occurred from Tetric EvoCeram and the least from Filtek Z250 (p < 0.05). LED and halogen light-curing units gave similar results for all RBCs (p > 0.05) except Tetric EvoCeram which showed greater elution for the LED unit (p < 0.05). TEGDMA was below the limit of quantification. HEMA eluted in similar concentrations from Filtek Supreme and Tetric EvoCeram (p > 0.05). SIGNIFICANCE The two nanohybrid RBCs eluted more cross-linking monomers than the ormocer and the control microhybrid RBC. Continuous elution over 28 days indicates that RBCs act as a chronic source of monomers in clinical conditions. Light source may affect monomer elution since differences were found for one out of four RBCs. Mathematical models for elution kinetics of UDMA and BisGMA indicated two elution mechanisms.

Determination of carbendazim residues in fruit juices by liquid chromatography-tandem mass spectrometry

In this paper a rapid optimized method for routine analysis of carbendazim residues in fruit juices is reported. The procedure is based on matrix solid-phase dispersion (MSPD) with diatomaceous earth and analysis of the extract by liquid chromatography-tandem mass spectrometry, with electrospray ionization (LC–ESI-MS/MS). In the method optimization, finding of the optimal pH for the extraction of carbendazim from juice was particularly critical. Significant matrix effects were observed, but could be eliminated using matrix-matched standards. High recoveries (82–102%), good repeatability (RSD ≤ 12%) and low limits of detection (0.03 ng ml−1) and quantification (0.1 ng ml−1) were achieved with this method.

Mathematical modeling of cross-linking monomer elution from resin-based dental composites †

Elution of potentially toxic substances, including monomers, from resin-based dental composites may affect the biocompatibility of these materials in clinical conditions. In addition to the amounts of eluted monomers, mathematical modeling of elution kinetics reveals composite restorations as potential chronic sources of leachable monomers. The aim of this work was to experimentally quantify elution of main cross-linking monomers from four commercial composites and offer a mathematical model of elution kinetics. Composite samples (n = 7 per group) of Filtek Supreme XT (3M ESPE), Tetric EvoCeram (Ivoclar Vivadent), Admira (Voco), and Filtek Z250 (3M ESPE) were prepared in 2-mm thick Teflon moulds and cured with halogen or light-emitting diode light. Monomer elution in ethanol and water was analyzed using high-performance liquid chromatography up to 28 days postimmersion. The mathematical model was expressed as a sum of two exponential regression functions representing the first-order kinetics law. Elution kinetics in all cases followed the same mathematical model though differences in rate constants as well as the extent of monomer elution were material-, LCU-, medium-dependent. The proposed mechanisms of elution indicate fast elution from surface and subsurface layers and up to 100 times slower monomer extraction from the bulk polymer.

Pharmaceutical residues in the Danube River Basin in Serbia - a two-year survey.

Pharmaceuticals are emerging contaminants with damaging effects to the environment and human health. Their presence in surface and especially groundwaters is regarded as detrimental, as they can ultimately reach drinking water. The aim of this work was to monitor pharmaceutical contamination of the Danube River and its tributaries in Serbia, and to assess the potential of their passing through all natural filtrations and reaching the groundwater. A total of 70 surface and groundwater samples was collected at 38 sampling sites at the Danube in Serbia. They were taken in five sampling campaigns performed in summer and autumn of 2009 and winter, spring and autumn of 2010. Samples were analyzed using a previously developed method which includes solid-phase extraction followed by liquid chromatography-tandem mass spectrometry.

Methods for monitoring of pesticide residues in water: current status and recent trends

An overview of analytical methods currently used for the determination of pesticide residues in water samples is presented. As liquid chromatography and gas chromatography, coupled to mass spectrometry, are considered to be the most appropriate techniques for determination of pesticides in environmental waters, the most recent developments and applications in this field are discussed, as well as the extraction procedures employed for analyte isolation and preconcentration.

FORCED DEGRADATION STUDY OF TORASEMIDE: CHARACTERIZATION OF ITS DEGRADATION PRODUCTS

Torasemide was subjected to forced degradation studies. Stress conditions were varied concerning hydrolysis (acid, base, and neutral), oxidation, photolysis, and thermal degradation in order to identify the potential degradation products and consequently establish the possible degradation pathways and intrinsic stability of the drug. The study was performed according to ICH guidelines and drug was found to be relatively stable in the solid form. It showed that torasemide degraded significantly under acidic, neutral and alkaline conditions and resulted in formation of degradation product R2. When temperature was increased the degradation was accelerated. Also, the drug showed slight instability under extreme oxidative stress conditions which resulted in formation of two degradation products in total. The drug and degradation products have been separated employing gradient elution method on Zorbax SB C18 analytical column. To characterize the degradation products LC–MSn was applied. The mass fragmentation pattern was established using single quadrupole and ion trap mass analyzers. Finally, the most possible degradation mechanism of torasemide in different experimental conditions was proposed.

Chemometrically Assisted Development and Validation of LC–UV and LC–MS Methods for Simultaneous Determination of Torasemide and its Impurities

Complete evaluation of chromatographic behavior and establishment of optimal experimental conditions for determination of torasemide and its four impurities are determined by experimental design. Fractional factorial and 3(n) full factorial design were employed for efficient and rapid optimization of liquid chromatography-ultraviolet and liquid chromatography-mass spectrometry (LC-MS) methods. Separation is achieved on a Zorbax SB C(18) analytical column (250 x 4.6 mm, 5 µm) with mobile phase consisting of acetonitrile and 10 mM ammonium formate (pH 2.5 with formic acid) in gradient mode. The flow rate is 1 mL min(-1), the temperature of the column is 25 °C and UV detection is performed at 290 nm. The efficiency of ionization in electrospray ionization is higher than in atmospheric pressure chemical ionization mode; therefore, it is further used for analysis of torasemide and its impurities. Both methods meet all validation criteria. The calibration curves show high linearity with the coefficients of correlation (r) greater than 0.9982. The obtained recovery values (95.78-104.92%) and relative standard deviation values (0.12-5.56%) indicate good accuracy and precision. Lower limit of detection (LOD) and limit of quantitation (LOQ) values are obtained with the LC-MS method, indicating higher sensitivity of the proposed method.

IMPURITY PROFILING OF MYCOPHENOLATE MOFETIL WITH THE ASSISSTANCE OF DESIRABILITY FUNCTION IN METHOD DEVELOPMENT

Multicriteria decision making methodology in combination with experimental design has been applied for optimization of stability-indicating LC/DAD method of Mycophenolate mofetil and its degradation products. Via fractional factorial design variables with statistically significant impact on retention parameters of the investigated substances were defined and then thoroughly optimized toward four chromatographic responses combining central composition design and desirability function. The separation was achieved on Chromolith column (C18e, 100 × 4.6 mm) with the mobile phase consisted of acetonitrile—0.015 M KH2PO4 (pH 4.4) (28:72, v/v). The flow rate of the mobile phase was 2 mL/min and the detection was performed using PDA detector at 215 nm. The method has been suitably modified for LC/MS/MS analysis. The ammonium-acetate buffer was used instead of phosphate buffer and pH of the water phase was adjusted with acetic acid. The flow rate was 1 mL min−1. The substance was subjected to stress conditions (0.01 M NaOH, 1 M HCl, 3–30% H2O2, 70°C and day light). It resulted in formation of Mycophenolic acid and two oxidation products. The substance showed to be stable only towards photolysis. The LC/MS/MS values and fragmentation pattern of two unknown oxidation products were used in its characterization.