Pesticides, which are widely used in agriculture to increase production or protect crop, are know... more Pesticides, which are widely used in agriculture to increase production or protect crop, are known to be potentially dangerous to consumers. Therefore oranges from local supermarket were analysed by the LC-ESI-MS method to determine the presence of pesticides. Two pesticides - thiabendazole and imazalil - were found in the oranges. Both are post-harvest pesticides. Analyses showed that these pesticides are
European journal of mass spectrometry (Chichester, England), 2012
Liquid chromatography electrospray ionization mass-spectrometry (LC-ESI-MS) was used to analyze 9... more Liquid chromatography electrospray ionization mass-spectrometry (LC-ESI-MS) was used to analyze 9-fluorenylmethylmethoxycarbonyl chloride (Fmoc-Cl) and diethyl ethoxymethylenemalonate (Deemm) derivatives of three amino acids and five other compounds. Influence of boric acid on their ionization was investigated and dramatic impact on the signal was observed. The strongest signal suppression (6% of signal remains) was observed for the Deemm derivative of beta-Alanine (with ammonium acetate in eluent). With only formic acid as the eluent pH modifier, signal enhancement was observed, being largest for Fmoc-Cl derivative of Phenylalanine, 267%. Investigation of the influence of boric acid shows that it is a possible signal enhancer for LC-ESI-MS analysis.
The matrix effects in HPLC/electrospray ionization (ESI)-MS analysis are difficult to compensate ... more The matrix effects in HPLC/electrospray ionization (ESI)-MS analysis are difficult to compensate for because of their large variability. It is, therefore, often more practical to include uncertainty due to the matrix effect into the uncertainty budget rather than try to compensate. This work presents an empirical approach--the matrix effect graph approach--for estimating the uncertainty due to the matrix effect in HPLC/ESI-MS analysis of pesticide residues in fruits and vegetables. At certain time intervals (1 month), a calibration graph using extracts of different fruits/vegetables as calibration solutions is prepared, and a regression line is fitted through these data. These fruits/vegetables may be either from the commodity group of the samples or from different commodity groups. The relative residuals of the calibration point peak areas are calculated and plotted against the measurement time. We term the resulting graph the matrix effect graph. The root mean square of the relati...
Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in... more Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography-tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.
Derivatization is one of the most common ways for improving chromatographic separation and sensit... more Derivatization is one of the most common ways for improving chromatographic separation and sensitivity for LC-ESI-MS analysis. The aim of this work was to design new derivatization reagents for LC-ESI-MS analysis of amino acids which would (1) provide good reversed phase chromatographic separation, (2) most importantly, provide low detection limits, (3) be easily synthesized, (4) produce derivatives which are less susceptible to matrix influences and (5) have convenient derivatization procedure with stable derivatives suitable for automatization. In the current work two new LC-ESI-MS compatible derivatization reagents have been designed and synthesized, dibenzyl ethoxymethylene malonate (DBEMM) and benzyl ethyl ethoxymethylene malonate (EBEMM). The DBEMM meets all the goals set with instrumental detection limits as low as 1 femtomole for amino acids and 40 attomole for selenoamino acids.
A density functional theory (B3LYP/6-311+G**), ab initio (HF/3-21G*), and semiempirical (PM3) stu... more A density functional theory (B3LYP/6-311+G**), ab initio (HF/3-21G*), and semiempirical (PM3) study of intrinsic basicities, protonation energies, or protonation enthalpies of organic phosphorus imine (iminophosphorane) including phosphazene, phosphorus ylide ( ...
A simple method to identify and determine Selenomethionine (SeMet) and Selenomethylselenocysteine... more A simple method to identify and determine Selenomethionine (SeMet) and Selenomethylselenocysteine (Se-MeSeCys) with diethyl ethoxymethylenemalonate (DEEMM) derivatization and LC-ESI-MS/MS determination was developed. Separation of SeMet and Se-MeSeCys was achieved in 15.3 minutes. The calibration graph was linear in the range of 0.32 pmol to 49 pmol for SeMet and 0.34 pmol to 40 pmol for Se-MeSeCys. To prevent oxidation of SeMet, 2-mercaptoethanol was introduced to the calibration solutions. Detection limits were 0.1 pmol, which are comparable to LC-ICP-MS analysis. The developed method therefore offers an alternative to LC-ICP-MS offering similar sensitivity and additionally allows identification. The method was used to determine Se-MeSeCys and SeMet in onion samples.
Glyphosate is one of the most common pesticides used in the pre-harvest treatment of cereals. Thi... more Glyphosate is one of the most common pesticides used in the pre-harvest treatment of cereals. This paper examines the matrix effect of glyphosate liquid chromatography/electrospray ionization mass spectrometric (LC/ESI-MS) analysis in wheat and rye. The matrix effect (ionization suppression) was found to be dependent on sample particle size taken for the extraction. If samples are ground to very small particles severe ionization suppression occurs. For lower glyphosate contents (<1 mg/kg) the signal may even be suppressed by more than 90%. The matrix effect was found to be dependent on the matrix - rye showed significantly stronger ionization suppression than wheat, although these matrices are not very different. The matrix effect also depends on the concentration of glyphosate in the post-extraction spiked samples. It is demonstrated that the isotope-labelled standard (13)C(2)-glyphosate undergoes different ionization suppression than glyphosate and is therefore not efficient in compensating for matrix effect. At the same time the extrapolative dilution approach allows to efficiently compensate for matrix effect.
An approach that allows setting up under predefined ionization conditions a rugged self-consisten... more An approach that allows setting up under predefined ionization conditions a rugged self-consistent quantitative experimental scale of electrospray ionization (ESI) efficiencies of organic compounds is presented. By ESI ionization efficiency (IE) we mean the efficiency of generating gas-phase ions from analyte molecules or ions in the ESI source. The approach is based on measurement of relative ionization efficiency (RIE) of two compounds (B1 and B2) by infusing a solution containing both compounds at known concentrations (C1 and C2) and measuring the mass-spectrometric responses of the protonated forms of the compounds (R1 and R2). The RIE of B1 and B2 is expressed as logRIE(B1, B2) = log[(R1 . C2)/(C1 . R2)]. The relative way of measurement leads to cancellation of many of the factors affecting IE (ESI source design, voltages in the source and ion transport system, solvent composition, flow rates and temperatures of the nebulizing and drying gases). Using this approach an ESI IE scale containing ten compounds (esters and aromatic amines) and spanning over 4 logRIE units has been compiled. The consistency of the scale (the consistency standard deviation of the scale is s = 0.16 logRIE units) was assured by making measurements using different concentration ratios (at least 6-fold concentration ratio range) of the compounds and by making circular validation measurements (the logRIE of any two compounds was checked by measuring both against a third compound).
Matrix effect (ME) - ionisation suppression or enhancement - in liquid chromatography/electrospra... more Matrix effect (ME) - ionisation suppression or enhancement - in liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) is caused by matrix components co-eluting with the analytes. ME has a complex and not fully understood nature. ME is also highly variable from sample to sample making it difficult to compensate for. In this work it was studied whether the background ion signals in scanned mass spectra of the LC effluent at the retention time of the analyte offer some insight into the presence and extent of matrix effect. Matrix effects for six pesticides - thiabendazole, carbendazime, methomyl, aldicarb, imazalil and methiocarb - in garlic and onion samples used in the study varied from 1% (suppression 99%) to 127% (enhancement 27%) depending on the pesticide and sample. Also standards in solvent and solvent blanks were included in the study. The ions most strongly varying from sample to sample - and therefore best describing the changes in sample composition and ME - were selected for quantification according to principal component analysis (PCA) for all six pesticides under study. These ions were used to account for ME via partial least-squares (PLS) regression. The calibration set was constructed from 19 samples and standards and the obtained calibration function was validated with seven samples and standards. The average errors from the test set were from 0.05 to 0.27 mg/kg for carbendazim and imazalil, respectively (the respective average pesticide concentrations were 0.22 and 0.88 mg/kg). The PLS results were significantly more accurate compared to the conventional solvent calibration resulting in average errors from 0.07 to 0.69 mg/kg for carbendazime and methiocarb, respectively.
Pesticides, which are widely used in agriculture to increase production or protect crop, are know... more Pesticides, which are widely used in agriculture to increase production or protect crop, are known to be potentially dangerous to consumers. Therefore oranges from local supermarket were analysed by the LC-ESI-MS method to determine the presence of pesticides. Two pesticides - thiabendazole and imazalil - were found in the oranges. Both are post-harvest pesticides. Analyses showed that these pesticides are
European journal of mass spectrometry (Chichester, England), 2012
Liquid chromatography electrospray ionization mass-spectrometry (LC-ESI-MS) was used to analyze 9... more Liquid chromatography electrospray ionization mass-spectrometry (LC-ESI-MS) was used to analyze 9-fluorenylmethylmethoxycarbonyl chloride (Fmoc-Cl) and diethyl ethoxymethylenemalonate (Deemm) derivatives of three amino acids and five other compounds. Influence of boric acid on their ionization was investigated and dramatic impact on the signal was observed. The strongest signal suppression (6% of signal remains) was observed for the Deemm derivative of beta-Alanine (with ammonium acetate in eluent). With only formic acid as the eluent pH modifier, signal enhancement was observed, being largest for Fmoc-Cl derivative of Phenylalanine, 267%. Investigation of the influence of boric acid shows that it is a possible signal enhancer for LC-ESI-MS analysis.
The matrix effects in HPLC/electrospray ionization (ESI)-MS analysis are difficult to compensate ... more The matrix effects in HPLC/electrospray ionization (ESI)-MS analysis are difficult to compensate for because of their large variability. It is, therefore, often more practical to include uncertainty due to the matrix effect into the uncertainty budget rather than try to compensate. This work presents an empirical approach--the matrix effect graph approach--for estimating the uncertainty due to the matrix effect in HPLC/ESI-MS analysis of pesticide residues in fruits and vegetables. At certain time intervals (1 month), a calibration graph using extracts of different fruits/vegetables as calibration solutions is prepared, and a regression line is fitted through these data. These fruits/vegetables may be either from the commodity group of the samples or from different commodity groups. The relative residuals of the calibration point peak areas are calculated and plotted against the measurement time. We term the resulting graph the matrix effect graph. The root mean square of the relati...
Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in... more Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography-tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.
Derivatization is one of the most common ways for improving chromatographic separation and sensit... more Derivatization is one of the most common ways for improving chromatographic separation and sensitivity for LC-ESI-MS analysis. The aim of this work was to design new derivatization reagents for LC-ESI-MS analysis of amino acids which would (1) provide good reversed phase chromatographic separation, (2) most importantly, provide low detection limits, (3) be easily synthesized, (4) produce derivatives which are less susceptible to matrix influences and (5) have convenient derivatization procedure with stable derivatives suitable for automatization. In the current work two new LC-ESI-MS compatible derivatization reagents have been designed and synthesized, dibenzyl ethoxymethylene malonate (DBEMM) and benzyl ethyl ethoxymethylene malonate (EBEMM). The DBEMM meets all the goals set with instrumental detection limits as low as 1 femtomole for amino acids and 40 attomole for selenoamino acids.
A density functional theory (B3LYP/6-311+G**), ab initio (HF/3-21G*), and semiempirical (PM3) stu... more A density functional theory (B3LYP/6-311+G**), ab initio (HF/3-21G*), and semiempirical (PM3) study of intrinsic basicities, protonation energies, or protonation enthalpies of organic phosphorus imine (iminophosphorane) including phosphazene, phosphorus ylide ( ...
A simple method to identify and determine Selenomethionine (SeMet) and Selenomethylselenocysteine... more A simple method to identify and determine Selenomethionine (SeMet) and Selenomethylselenocysteine (Se-MeSeCys) with diethyl ethoxymethylenemalonate (DEEMM) derivatization and LC-ESI-MS/MS determination was developed. Separation of SeMet and Se-MeSeCys was achieved in 15.3 minutes. The calibration graph was linear in the range of 0.32 pmol to 49 pmol for SeMet and 0.34 pmol to 40 pmol for Se-MeSeCys. To prevent oxidation of SeMet, 2-mercaptoethanol was introduced to the calibration solutions. Detection limits were 0.1 pmol, which are comparable to LC-ICP-MS analysis. The developed method therefore offers an alternative to LC-ICP-MS offering similar sensitivity and additionally allows identification. The method was used to determine Se-MeSeCys and SeMet in onion samples.
Glyphosate is one of the most common pesticides used in the pre-harvest treatment of cereals. Thi... more Glyphosate is one of the most common pesticides used in the pre-harvest treatment of cereals. This paper examines the matrix effect of glyphosate liquid chromatography/electrospray ionization mass spectrometric (LC/ESI-MS) analysis in wheat and rye. The matrix effect (ionization suppression) was found to be dependent on sample particle size taken for the extraction. If samples are ground to very small particles severe ionization suppression occurs. For lower glyphosate contents (<1 mg/kg) the signal may even be suppressed by more than 90%. The matrix effect was found to be dependent on the matrix - rye showed significantly stronger ionization suppression than wheat, although these matrices are not very different. The matrix effect also depends on the concentration of glyphosate in the post-extraction spiked samples. It is demonstrated that the isotope-labelled standard (13)C(2)-glyphosate undergoes different ionization suppression than glyphosate and is therefore not efficient in compensating for matrix effect. At the same time the extrapolative dilution approach allows to efficiently compensate for matrix effect.
An approach that allows setting up under predefined ionization conditions a rugged self-consisten... more An approach that allows setting up under predefined ionization conditions a rugged self-consistent quantitative experimental scale of electrospray ionization (ESI) efficiencies of organic compounds is presented. By ESI ionization efficiency (IE) we mean the efficiency of generating gas-phase ions from analyte molecules or ions in the ESI source. The approach is based on measurement of relative ionization efficiency (RIE) of two compounds (B1 and B2) by infusing a solution containing both compounds at known concentrations (C1 and C2) and measuring the mass-spectrometric responses of the protonated forms of the compounds (R1 and R2). The RIE of B1 and B2 is expressed as logRIE(B1, B2) = log[(R1 . C2)/(C1 . R2)]. The relative way of measurement leads to cancellation of many of the factors affecting IE (ESI source design, voltages in the source and ion transport system, solvent composition, flow rates and temperatures of the nebulizing and drying gases). Using this approach an ESI IE scale containing ten compounds (esters and aromatic amines) and spanning over 4 logRIE units has been compiled. The consistency of the scale (the consistency standard deviation of the scale is s = 0.16 logRIE units) was assured by making measurements using different concentration ratios (at least 6-fold concentration ratio range) of the compounds and by making circular validation measurements (the logRIE of any two compounds was checked by measuring both against a third compound).
Matrix effect (ME) - ionisation suppression or enhancement - in liquid chromatography/electrospra... more Matrix effect (ME) - ionisation suppression or enhancement - in liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) is caused by matrix components co-eluting with the analytes. ME has a complex and not fully understood nature. ME is also highly variable from sample to sample making it difficult to compensate for. In this work it was studied whether the background ion signals in scanned mass spectra of the LC effluent at the retention time of the analyte offer some insight into the presence and extent of matrix effect. Matrix effects for six pesticides - thiabendazole, carbendazime, methomyl, aldicarb, imazalil and methiocarb - in garlic and onion samples used in the study varied from 1% (suppression 99%) to 127% (enhancement 27%) depending on the pesticide and sample. Also standards in solvent and solvent blanks were included in the study. The ions most strongly varying from sample to sample - and therefore best describing the changes in sample composition and ME - were selected for quantification according to principal component analysis (PCA) for all six pesticides under study. These ions were used to account for ME via partial least-squares (PLS) regression. The calibration set was constructed from 19 samples and standards and the obtained calibration function was validated with seven samples and standards. The average errors from the test set were from 0.05 to 0.27 mg/kg for carbendazim and imazalil, respectively (the respective average pesticide concentrations were 0.22 and 0.88 mg/kg). The PLS results were significantly more accurate compared to the conventional solvent calibration resulting in average errors from 0.07 to 0.69 mg/kg for carbendazime and methiocarb, respectively.
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