Svetlana Grujić

Determination of multiple pharmaceutical classes in surface and ground waters by liquid chromatography-ion trap-tandem mass spectrometry.

This paper describes development, optimization and application of analytical method for determination and reliable confirmation of nineteen pharmaceuticals from different therapeutic classes (antibiotics--beta-lactams, cephalosporines, sulfonamides, macrolides and tetracyclines; benzodiazepines; antiepileptics and analgoantipyretics) in surface and ground waters at ng l(-1) levels. Water samples were prepared using solid-phase extraction and extracts were analyzed by liquid chromatography-ion trap-tandem mass spectrometry with electrospray ionization in both positive and negative ionization mode. The efficiency of ten different SPE cartridges to extract diverse compounds from water was tested. The pH-value of the water sample, the volume of elution solvent and the sample volume were optimized. Matrix effect, especially pronounced for cephalexin and metamizole, was eliminated using matrix-matched standards. It was determined that extraction should be performed at pH approximately 7.5, i.e. without pH adjustment, and at pH 3, depending on the analyte. Azithromycin, doxycycline and acetylsalicylic acid must be extracted in acidic environment, whereas extraction of paracetamol, ampicillin, erythromycin and metamizole should be performed without pH adjustment. Repeatability of the method was generally lower than 20%. The estimated limits of detection were in the range from 0.15 to 12.46 ng l(-1). The method was applied to 26 water samples for monitoring of selected drug residues. Results revealed the presence of carbamazepine (80% of water samples), azithromycin (23%), as well as trimethoprim and paracetamol (both 15%). The most striking was the false positive signal of diclofenac in every analyzed water sample. Confirmation of the positive results was performed by repeated injection of the positive sample extracts using confirmatory method with additional transitions.

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.

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.

Trace analysis of selected hormones and sterols in river sediments by liquid chromatography-atmospheric pressure chemical ionization–tandem mass spectrometry

In this paper, development and optimization of new LC-MS method for determination of twenty selected hormones, human/animal and plant sterols in river sediments were described. Sediment samples were prepared using ultrasonic extraction and clean up with silica gel/anhydrous sodium sulphate cartridge. Extracts were analyzed by liquid chromatography-linear ion trap-tandem mass spectrometry, with atmospheric pressure chemical ionization. The optimized extraction parameters were extraction solvent (methanol), weight of the sediment (2 g) and time of ultrasonic extraction (3× 10 min). Successful chromatographic separation of hormones (estriol and estrone, 17α- and 17β-estradiol) and four human/animal sterols (epicoprostanol, coprostanol, α-cholestanol and β-cholestanol) that have identical fragmentation reactions was achieved. The developed and optimized method provided high recoveries (73-118%), low limits of detection (0.8-18 ng g(-1)) and quantification (2.5-60 ng g(-1)) with the RSDs generally lower than 20%. Applicability of the developed method was confirmed by analysis of six river sediment samples. A widespread occurrence of human/animal and plant sterols was found. The only detected hormone was mestranol in just one sediment sample.

Release behaviour of carbamazepine-loaded poly(ε-caprolactone)/poly(ethylene oxide) microspheres

Poly(ε-caprolactone) (PCL), a biodegradable and biocompatible aliphatic polyester has a great potential as a drug carrying material in controlled drug delivery/release systems. The most simple and economical way to tailor the release profile of active substances from biodegradable polymer matrix is by the addition of the second polymeric component in the polymer matrix, i.e. by blending. This study describes the preparation and characterization of a carbamazepine-loaded microspheres by the use of PCL blended with poly(ethylene oxide) as a drug carrying material. By the use of two-component hydrophilic/hydrophobic polymer blend as a microspheres’ matrix material, release profile of the drug can be modified and dictated. The microspheres prepared by classical oil-in-water emulsion solvent evaporation technique were characterized with respect to particle size and morphology, polymer matrix composition, encapsulation efficiency, physical state of the drug and in vitro release behaviour. It was presented that the release profile can be modified by the presence and the amount of hydrophilic component in the starting formulation of microspheres.

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.

Determination of anisomycin in tissues and serum by LC-MS/MS: application to pharmacokinetic and distribution studies in rats

A selective, sensitive and fast method for extraction, identification and quantification of multifunctional drug anisomycin in various tissues and serum, based on liquid chromatography-tandem mass spectrometry, was developed, optimized and validated. The method was validated according to the FDA guidelines and generally demonstrated good selectivity, accuracy, precision, and stability of the analyte. In the optimized method, high extraction efficiency was achieved for tested tissues (heart, brain, spleen, kidney, liver and femoral muscle) and serum. The obtained values of lower limits of quantification (LLOQ, 1.0–11.0 ng g−1) and limits of detection (0.3–3.3 ng g−1) indicated that the method was suitable for determination of trace levels of anisomycin in the complex matrices. The method was linear (R2 ≥ 0.990) in the tested concentration range (LLOQ–2500 ng g−1). The developed method was successfully applied in the first study on in vivo pharmacokinetics and distribution of anisomycin in tissues and serum of Wistar albino rats following subcutaneous injection (150 mg kg−1). The peak concentration in most tissues was achieved within 3 h after injection. The highest anisomycin concentration was found in the brain and the lowest concentration was found in the serum.