Removal of potentially genotoxic acetamide and arylsulfonate impurities from crude drugs by molecular imprinting.

The present study describes the synthesis and preliminary testing of molecularly imprinted polymers (MIPs) as scavenger resins for removal of the genotoxic impurities (GTI) acetamide and arylsulfonates from active pharmaceutical ingredients (API). The MIPs were synthesized as monoliths using acetamide or methyl tosylate respectively as templates. The polymers were crushed and subsequently tested in the batch and chromatographic mode for template recognition and potential removal efficiency. Both the acetamide and the tosylate MIPs exhibited a strong memory effect for their templates and selectivity with respect to model APIs. For instance the MIP for acetamide preferentially retained acetamide over other amides, such as formamide, acrylamide, methacrylamide, benzamide and N-tert-butylacrylamide. Moreover, passing model API crude contaminated with the acetamide through the MIPs led to the quantitative removal of acetamide.

Cloud point extraction with Triton X-114 for separation of metsulfuron-methyl, chlorsulfuron, and bensulfuron-methyl from water, soil, and rice and analysis by high-performance liquid chromatography.

A new and efficient analytic methodology based on cloud point extraction (CPE) was developed for determination of pesticide residues of metsulfuron-methyl (MSM), chlorsulfuron (CS), and bensulfuron-methyl (BSM) in water, soil, and rice grain by high-performance liquid chromatography (HPLC). Multiple experimental conditions that affected CPE efficiency-including surfactant type and concentration, equilibration temperature and duration, ionic strength, and solution pH were identified. CPE conditions were optimized as follows: 1.5% Triton X-114 (w/v), 12% Na(2)SO(4) (w/v) solution (pH 2.0), and heat-assisted at 50 °C for 15 min. The calibration curves for all analytes were linear, ranging from 0.05 to 4.0 mg L(-1), with the correlation coefficients >0.9995 by HPLC-ultraviolet detector and were linear, ranging from 0.004 to 2.0 mg L(-1), with correlation coefficients >0.9983 by CPE-HPLC. The average recoveries at the three spiked levels using CPE ranged from 86.0% to 94.5% for water samples with relative SDs (RSDs) of 0.4% to approximately 7.8%; from 85.6% to 94.8% for soil samples with RSDs of 1.2% to approximately 9.5%; and from 81.9% to 91.3% for rice samples with RSDs of 1.7% to approximately 5.8%. The proposed CPE-HPLC method can be successfully used to analyze MSM, CS, and BSM residues from contaminated water, soil, and rice grain samples.

A simple and fast method for chlorsulfuron and metsulfuron methyl determination in water samples using multiwalled carbon nanotubes (MWCNTs) and capillary electrophoresis.

A new method to determine metsulfuron methyl (MSM) and chlorsulfuron (CS) in different water samples was developed. It consists in a solid phase extraction (SPE) procedure using multiwalled carbon nanotubes (MWCNTs) as sorbent material in combination with capillary zone electrophoretic determination. To carry out the pre-concentration step, a simple flow injection system was developed and optimized. Thus, 250 µL of aqueous solution containing methanol 50% (v/v) and acetonitrile 2% (v/v) as eluent, 10 mL of sample and a flow rate of 1.15 mL min(-1) were selected. The CE variables also were optimized. A rapid determination and good resolution of two herbicides were obtained within 9 min using a simple electrophoretic buffer (50 mmol L(-1) sodium tetraborate with 3% of methanol, pH=9.0). Under the optimum conditions, the calibration curves were linear between 0.5 and 6 µg L(-1) for MSM and CS with R(2)=0.995 and 0.997, respectively. The repeatability of the proposed method, expressed as relative standard deviation (RSD), varied between 4.1% and 5.4% (n=10) and the detection limits for MSM and CS were 0.40 and 0.36 µg L(-1), respectively. Good results were achieved when the proposed method was applied to spiked real water samples. The recoveries percentages of the two analytes were over the range 86-108%.

Celtisanin, a novel sulphonated phenolic from Celtis australis L. fruits.

A novel sulphonated phenolic named celtisanin, elucidated as 3-[8'-hydroxy-prop-6'-ene-6'-yl]-5-hydroxymethyl-4-methoxy-2-[penta-1',4'-diene-1'-yl-5'-sulphonic acid]-5,6-dihydrobenzofuran, has been isolated from the fruits of Celtis australis (Ulmaceae), together with three known compounds: apigenin, quercetin and its glucoside. Their structures were characterised by means of chemical and spectral methods, including advanced 2-D nuclear magnetic resonance (NMR) studies.

Sorption of anionic metsulfuron-methyl and cationic difenzoquat on peat and soil as affected by copper.

The effect of cationic copper (Cu2+) on the sorption of anionic metsulfuron-methyl (Me) and cationic difenzoquat (DZ) to peat and soil was studied using a batch equilibration method. The results showed that Cu2+ increased the sorption of Me but diminished the sorption of DZ. The adsorption of Cu2+ on the surface of peat and soil neutralizes the negative charge, making the zeta potential (zeta) of peat and soil less negative, consequently decreasing the repulsion between the surface of peat or soil and Me and increasing the sorption of Me. Cu2+ may additionally form Cu-Me complexes in aqueous solution, which was preferentially sorbed to peat and soil over the anionic Me. In contrast, the decreased negative surface charge of soil and peat does not favor the sorption of cationic DZ. Fourier transform infrared showed that DZ may be sorbed through interaction with -OH or -COOH groups of peat and soil and that surface complexes of Cu2+ may form through these groups. A competitive sorption between Cu2t and DZ for the same sorption sites is indicated, leading to mutual sorption inhibition of both cations.

Theory and use of the pseudophase model in gas-liquid chromatographic enantiomeric separations.

The theory and use of the "three-phase" model in enantioselective gas-liquid chromatography utilizing a methylated cyclodextrin/polysiloxane stationary phase is presented for the first time. Equations are derived that account for all three partition equilibria in the system, including partitioning between the gas mobile phase and both stationary-phase components and the analyte equilibrium between the polysiloxane and cyclodextrin pseudophase. The separation of the retention contributions from the achiral and chiral parts of the stationary phase can be easily accomplished. Also, it allows the direct examination of the two contributions to enantioselctivity, i.e., that which occurs completely in the liquid stationary phase versus the direct transfer of the chiral analyte in the gas phase to the dissolved chiral selector. Six compounds were studied to verify the model: 1-phenylethanol, alpha-ionone, 3-methyl-1-indanone, o-(chloromethyl)phenyl sulfoxide, o-(bromomethyl)phenyl sulfoxide, and ethyl p-tolylsulfonate. Generally, the cyclodextrin component of the stationary phase contributes to retention more than the bulk liquid polysiloxane. This may be an important requirement for effective GC chiral stationary phases. In addition, the roles of enthalpy and entropy toward enantiorecognition by this stationary phase were examined. While enantiomeric differences in both enthalpy and entropy provide chiral discrimination, the contribution of entropy appears to be more significant in this regard. The three-phase model may be applied to any gas-liquid chromatography stationary phase involving a pseudophase.

Study of the elution mechanism of sodium aryl sulfonates on bare silica and a cyano bonded phase with methanol-modified carbon dioxide containing an ionic additive.

The elution mechanism of sodium sulfonates on both Deltabond cyanopropyl and bare silica stationary phases with an isocratic mobile phase composed of methanol-modified CO2 wherein an ammonium salt additive was dissolved in the methanol has been studied. The presence of the additive was crucial concerning elution of the sulfonate salts. Solid state 29silicon nuclear magnetic resonance spectroscopy provided some insight concerning the interaction of the mobile phase additive with the silica-based stationary phase. Computational calculations concerning the charge distribution on various ammonium salts were performed in an effort to explain the elution behavior. Ammonium ions are believed to deactivate available silanol sites on both phases. In addition, ammonium ion is speculated to interact with the cyano groups on the bonded phase. For concentrations of additive greater than 2 mM, stationary phase coverage of ammonium ion is anticipated to exceed one monolayer for both bare and bonded silica. The acetate counter-ion is thought to facilitate elution of the anionic sulfonates from the positively charged stationary phase in a pseudo ion exchange mechanism.

Isotachophoretic focusing and mass spectrometry detection as tools for improving the determination of aromatic sulfonates in capillary electrophoresis.

We explored isotachophoresis-capillary zone electrophoresis (ITP-CZE) with diode array detection on a single capillary to find out how to increase the injection volume and decrease the detection limits of aromatic sulfonates in CZE. The ITP was performed by applying a negative voltage in conjunction with hydrodynamic backpressure programming, and the terminating buffer was removed before the CZE separation, which resulted in highly sensitive determinations. The ITP increased the signal response of conventional hydrodynamic injection by a factor of 100, whereas the separation efficiency was unaffected. The limits of detection of the method were between 3 and 5 nugL(-1). The method was successfully used to determine these compounds in water samples. Experimental conditions for capillary electrophoresis-mass spectrometry were optimized and applied to determine aromatic sulfonates in water samples. These techniques enables the 2-naphthalenesulfonate to be determined in water samples.

Analysis of metsulfuron-methyl in soil by liquid chromatography/tandem mass spectrometry. Application to a field dissipation study.

An analytical method is described for the extraction of metsulfuron-methyl from soil at sub-parts per billion levels (LOQ = 0.2 microgram kg(-1)). The herbicide was quantitatively determined and identified by ESI LC/MS/MS. The method has been applied to a field dissipation study in which metsulfuron-methyl was applied to spring barley at three dosage rates: 4, 8, and 16 g of active ingredient ha(-)(1). The results of 2 years are presented. The dissipation rate of metsulfuron-methyl in topsoil was very rapid, with a calculated half-life of 6.5 days. Laboratory mineralization studies with native soils in contrast to autoclaved soils indicated that microbial degradation of (14)C-labeled metsulfuron-methyl and (14)C-labeled 2-amino-4-methoxy-6-methyl-1,3,5-triazine in soil microcosms is an important factor for the complete degradation of metsulfuron-methyl in the field. However, the mineralization rate of the sulfonamide was much higher.