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Hans H Maurer - One of the best experts on this subject based on the ideXlab platform.
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the role of human hepatic cytochrome p450 isozymes in the metabolism of racemic 3 4 methylenedioxyethylamphetamine and its single enantiomers
Drug Metabolism and Disposition, 2008Co-Authors: Markus R Meyer, Frank T Peters, Hans H MaurerAbstract:The 3,4-methylenedioxy-methamphetamine (MDMA)-related designer drug 3,4-methylenedioxyethylamphetamine (MDEA, Eve) is a chiral compound that is mainly metabolized by N-deethylation and demethylenation during phase I metabolism. The involvement of several cytochrome P450 (P450) isozymes in these metabolic steps has been demonstrated by inhibition assays using human liver microsomes. However, a comprehensive study on the involvement of all relevant human P450s has not been published yet. In addition, the chirality of this drug was not considered in these in vitro studies. The aim of the present work was first to elucidate the contribution of the relevant human P450 isozymes in the demethylenation as well as in the N-dealkylation of racemic MDEA and its single enantiomers and secondly to compare these findings with recently published data concerning the enantioselective metabolism of MDMA. Racemic MDEA and its single enantiomers were incubated using heterologously expressed human P450s, and the corresponding metabolites dihydroxyethylamphetamine and methylenedioxyamphetamine were determined by gas chromatography-mass spectrometry after chiral derivatization with S-heptafluorobutyrylprolyl chloride. The highest contributions to both metabolic steps as calculated from the enzyme kinetic data were obtained for CYP3A4 and CYP2D6 at substrate concentrations corresponding to plasma concentrations of recreational users after intake of racemic MDEA. Both metabolic reactions were found to be enantioselective with a general preference for the S-enantiomers, which was particularly pronounced in the case of CYP2C19. In conclusion, different pharmacokinetic properties of MDEA enantiomers observed in vivo are therefore partially caused by P450-dependent enantioselective metabolism.
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negative ion chemical ionization gas chromatography mass spectrometry assay for enantioselective measurement of amphetamines in oral fluid application to a controlled study with MDMA and driving under the influence cases
Clinical Chemistry, 2007Co-Authors: Frank T Peters, Nele Samyn, W J Riedel, Thomas Kraemer, Hans H MaurerAbstract:Background: Enantioselective analysis of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) helps interpret toxicological results. Methods have been described for various matrices, but so far not for oral fluid, a matrix of increasing importance in testing for drugs of abuse, especially in the context of driving under the influence of drugs (DUID). Methods: After dilution with 200 μL carbonate buffer (pH 9), oral fluid samples (10–50 μL) were derivatized with S -heptafluorobutyrylprolyl chloride. The resulting diastereomers were extracted into 100 μL of cyclohexane, separated by gas chromatography (HP-5MS column), and detected by mass spectrometry in the negative-ion chemical ionization mode (GC-NICI-MS). The method was validated and applied to samples from a controlled study with MDMA and from authentic DUID cases. Results: The derivatized AM, MA, MDA, MDMA, and MDEA enantiomers were well separated from each other. The method was linear from 5–250 μg/L per enantiomer of MDA and from 25–1250 μg/L per enantiomer of AM, MA, MDMA, and MDEA. With the exception of MDEA, analytical recoveries, repeatability, and intermediate precision were within required limits. The analyte concentrations and enantiomer ratios in the application samples correlated only weakly with corresponding published plasma data. Conclusions: This sensitive, reliable, and fast GC-NICI-MS assay enantioselectively measures AM, MA, MDA, and MDMA in oral fluid samples. Prediction of plasma concentrations and enantiomer ratios from respective oral fluid data is not possible.
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drug testing in blood validated negative ion chemical ionization gas chromatographic mass spectrometric assay for enantioselective measurement of the designer drugs mdea MDMA and mda and its application to samples from a controlled study with MDMA
Clinical Chemistry, 2005Co-Authors: Frank T Peters, Nele Samyn, Caroline T J Lamers, W J Riedel, Thomas Kraemer, Gert De Boeck, Hans H MaurerAbstract:Background: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA. Methods: The analytes were extracted from ≤0.2 mL of plasma by mixed-mode solid-phase extraction. After derivatization with S -(−)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in the negative-ion chemical ionization mode. The method was fully validated and applied to samples from a controlled study in which a single dose of racemic MDMA (75 mg) was administered. Results: The derivatized enantiomers were well separated and detected with good sensitivity. The assay was linear (per enantiomer) at 1–50 μg/L for MDA and 5–250 μg/L for MDMA and MDEA. Analytical recovery, accuracy, repeatability, and intermediate precision data were within required limits. Extraction yields were 82.1%–95.3%. In the study samples, concentrations of R -(−)-MDMA significantly exceeded those of S -(+)-MDMA. Their ratios ( R vs S ) were always >1.0 and increased over time. Concentrations of S -(+)-MDA exceeded those of R -(−)-MDA, their ratios ( R vs S ) also increasing over time but remaining Conclusions: This assay enables sensitive, reliable, and fast enantioselective measurement of MDA, MDMA, and MDEA in small volumes of plasma. The controlled study data confirm previous findings of MDMA and MDA enantiomer ratios ( R vs S ) increasing over time after ingestion of racemic MDMA.
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concentrations and ratios of amphetamine methamphetamine mda MDMA and mdea enantiomers determined in plasma samples from clinical toxicology and driving under the influence of drugs cases by gc nici ms
Journal of Analytical Toxicology, 2003Co-Authors: Frank T Peters, Nele Samyn, Thomas Kraemer, M Wahl, G De Boeck, Hans H MaurerAbstract:Enantiomers of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) exhibit different pharmacological properties. This may be important for the interpretation of analytical results. Plasma samples were analyzed using validated negative ion chemical ionization gas chromatography-mass spectrometry procedures. The results for clinical toxicology cases, divided into screening (SCR) and intoxication (ITX) cases, and those of driving under the influence of drugs (DUID) cases were compared. The concentrations of all enantiomers, except R-(-)-MDA and R-(-)- and S-(+)-MA, in the SCR samples were lower than in ITX and DUID samples. Differences between concentrations in ITX and DUID samples were only significant for both enantiomers of AM (DUID higher). These findings suggested impairment in drugged drivers. Different enantiomer ratios (R vs. S) were found for AM between DUID and SCR samples, for MDMA between ITX and SCR samples, and for MDA between DUID and ITX and DUID and SCR samples. Higher MDMA enantiomer ratios in SCR compared to ITX samples are in accordance with a previously described increase of those ratios over time, possibly allowing differentiation of recent from nonrecent ingestion. Pharmacokinetic analysis of a MDMA poisoning yielded elimination half-lives of 6.0 h for R-(-)-MDMA and 4.1 h for S-(+)-MDMA. The enantiomer ratios rose exponentially over time.
Frank T Peters - One of the best experts on this subject based on the ideXlab platform.
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the role of human hepatic cytochrome p450 isozymes in the metabolism of racemic 3 4 methylenedioxyethylamphetamine and its single enantiomers
Drug Metabolism and Disposition, 2008Co-Authors: Markus R Meyer, Frank T Peters, Hans H MaurerAbstract:The 3,4-methylenedioxy-methamphetamine (MDMA)-related designer drug 3,4-methylenedioxyethylamphetamine (MDEA, Eve) is a chiral compound that is mainly metabolized by N-deethylation and demethylenation during phase I metabolism. The involvement of several cytochrome P450 (P450) isozymes in these metabolic steps has been demonstrated by inhibition assays using human liver microsomes. However, a comprehensive study on the involvement of all relevant human P450s has not been published yet. In addition, the chirality of this drug was not considered in these in vitro studies. The aim of the present work was first to elucidate the contribution of the relevant human P450 isozymes in the demethylenation as well as in the N-dealkylation of racemic MDEA and its single enantiomers and secondly to compare these findings with recently published data concerning the enantioselective metabolism of MDMA. Racemic MDEA and its single enantiomers were incubated using heterologously expressed human P450s, and the corresponding metabolites dihydroxyethylamphetamine and methylenedioxyamphetamine were determined by gas chromatography-mass spectrometry after chiral derivatization with S-heptafluorobutyrylprolyl chloride. The highest contributions to both metabolic steps as calculated from the enzyme kinetic data were obtained for CYP3A4 and CYP2D6 at substrate concentrations corresponding to plasma concentrations of recreational users after intake of racemic MDEA. Both metabolic reactions were found to be enantioselective with a general preference for the S-enantiomers, which was particularly pronounced in the case of CYP2C19. In conclusion, different pharmacokinetic properties of MDEA enantiomers observed in vivo are therefore partially caused by P450-dependent enantioselective metabolism.
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negative ion chemical ionization gas chromatography mass spectrometry assay for enantioselective measurement of amphetamines in oral fluid application to a controlled study with MDMA and driving under the influence cases
Clinical Chemistry, 2007Co-Authors: Frank T Peters, Nele Samyn, W J Riedel, Thomas Kraemer, Hans H MaurerAbstract:Background: Enantioselective analysis of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) helps interpret toxicological results. Methods have been described for various matrices, but so far not for oral fluid, a matrix of increasing importance in testing for drugs of abuse, especially in the context of driving under the influence of drugs (DUID). Methods: After dilution with 200 μL carbonate buffer (pH 9), oral fluid samples (10–50 μL) were derivatized with S -heptafluorobutyrylprolyl chloride. The resulting diastereomers were extracted into 100 μL of cyclohexane, separated by gas chromatography (HP-5MS column), and detected by mass spectrometry in the negative-ion chemical ionization mode (GC-NICI-MS). The method was validated and applied to samples from a controlled study with MDMA and from authentic DUID cases. Results: The derivatized AM, MA, MDA, MDMA, and MDEA enantiomers were well separated from each other. The method was linear from 5–250 μg/L per enantiomer of MDA and from 25–1250 μg/L per enantiomer of AM, MA, MDMA, and MDEA. With the exception of MDEA, analytical recoveries, repeatability, and intermediate precision were within required limits. The analyte concentrations and enantiomer ratios in the application samples correlated only weakly with corresponding published plasma data. Conclusions: This sensitive, reliable, and fast GC-NICI-MS assay enantioselectively measures AM, MA, MDA, and MDMA in oral fluid samples. Prediction of plasma concentrations and enantiomer ratios from respective oral fluid data is not possible.
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drug testing in blood validated negative ion chemical ionization gas chromatographic mass spectrometric assay for enantioselective measurement of the designer drugs mdea MDMA and mda and its application to samples from a controlled study with MDMA
Clinical Chemistry, 2005Co-Authors: Frank T Peters, Nele Samyn, Caroline T J Lamers, W J Riedel, Thomas Kraemer, Gert De Boeck, Hans H MaurerAbstract:Background: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA. Methods: The analytes were extracted from ≤0.2 mL of plasma by mixed-mode solid-phase extraction. After derivatization with S -(−)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in the negative-ion chemical ionization mode. The method was fully validated and applied to samples from a controlled study in which a single dose of racemic MDMA (75 mg) was administered. Results: The derivatized enantiomers were well separated and detected with good sensitivity. The assay was linear (per enantiomer) at 1–50 μg/L for MDA and 5–250 μg/L for MDMA and MDEA. Analytical recovery, accuracy, repeatability, and intermediate precision data were within required limits. Extraction yields were 82.1%–95.3%. In the study samples, concentrations of R -(−)-MDMA significantly exceeded those of S -(+)-MDMA. Their ratios ( R vs S ) were always >1.0 and increased over time. Concentrations of S -(+)-MDA exceeded those of R -(−)-MDA, their ratios ( R vs S ) also increasing over time but remaining Conclusions: This assay enables sensitive, reliable, and fast enantioselective measurement of MDA, MDMA, and MDEA in small volumes of plasma. The controlled study data confirm previous findings of MDMA and MDA enantiomer ratios ( R vs S ) increasing over time after ingestion of racemic MDMA.
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concentrations and ratios of amphetamine methamphetamine mda MDMA and mdea enantiomers determined in plasma samples from clinical toxicology and driving under the influence of drugs cases by gc nici ms
Journal of Analytical Toxicology, 2003Co-Authors: Frank T Peters, Nele Samyn, Thomas Kraemer, M Wahl, G De Boeck, Hans H MaurerAbstract:Enantiomers of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) exhibit different pharmacological properties. This may be important for the interpretation of analytical results. Plasma samples were analyzed using validated negative ion chemical ionization gas chromatography-mass spectrometry procedures. The results for clinical toxicology cases, divided into screening (SCR) and intoxication (ITX) cases, and those of driving under the influence of drugs (DUID) cases were compared. The concentrations of all enantiomers, except R-(-)-MDA and R-(-)- and S-(+)-MA, in the SCR samples were lower than in ITX and DUID samples. Differences between concentrations in ITX and DUID samples were only significant for both enantiomers of AM (DUID higher). These findings suggested impairment in drugged drivers. Different enantiomer ratios (R vs. S) were found for AM between DUID and SCR samples, for MDMA between ITX and SCR samples, and for MDA between DUID and ITX and DUID and SCR samples. Higher MDMA enantiomer ratios in SCR compared to ITX samples are in accordance with a previously described increase of those ratios over time, possibly allowing differentiation of recent from nonrecent ingestion. Pharmacokinetic analysis of a MDMA poisoning yielded elimination half-lives of 6.0 h for R-(-)-MDMA and 4.1 h for S-(+)-MDMA. The enantiomer ratios rose exponentially over time.
Nele Samyn - One of the best experts on this subject based on the ideXlab platform.
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negative ion chemical ionization gas chromatography mass spectrometry assay for enantioselective measurement of amphetamines in oral fluid application to a controlled study with MDMA and driving under the influence cases
Clinical Chemistry, 2007Co-Authors: Frank T Peters, Nele Samyn, W J Riedel, Thomas Kraemer, Hans H MaurerAbstract:Background: Enantioselective analysis of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) helps interpret toxicological results. Methods have been described for various matrices, but so far not for oral fluid, a matrix of increasing importance in testing for drugs of abuse, especially in the context of driving under the influence of drugs (DUID). Methods: After dilution with 200 μL carbonate buffer (pH 9), oral fluid samples (10–50 μL) were derivatized with S -heptafluorobutyrylprolyl chloride. The resulting diastereomers were extracted into 100 μL of cyclohexane, separated by gas chromatography (HP-5MS column), and detected by mass spectrometry in the negative-ion chemical ionization mode (GC-NICI-MS). The method was validated and applied to samples from a controlled study with MDMA and from authentic DUID cases. Results: The derivatized AM, MA, MDA, MDMA, and MDEA enantiomers were well separated from each other. The method was linear from 5–250 μg/L per enantiomer of MDA and from 25–1250 μg/L per enantiomer of AM, MA, MDMA, and MDEA. With the exception of MDEA, analytical recoveries, repeatability, and intermediate precision were within required limits. The analyte concentrations and enantiomer ratios in the application samples correlated only weakly with corresponding published plasma data. Conclusions: This sensitive, reliable, and fast GC-NICI-MS assay enantioselectively measures AM, MA, MDA, and MDMA in oral fluid samples. Prediction of plasma concentrations and enantiomer ratios from respective oral fluid data is not possible.
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drug testing in blood validated negative ion chemical ionization gas chromatographic mass spectrometric assay for enantioselective measurement of the designer drugs mdea MDMA and mda and its application to samples from a controlled study with MDMA
Clinical Chemistry, 2005Co-Authors: Frank T Peters, Nele Samyn, Caroline T J Lamers, W J Riedel, Thomas Kraemer, Gert De Boeck, Hans H MaurerAbstract:Background: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA. Methods: The analytes were extracted from ≤0.2 mL of plasma by mixed-mode solid-phase extraction. After derivatization with S -(−)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in the negative-ion chemical ionization mode. The method was fully validated and applied to samples from a controlled study in which a single dose of racemic MDMA (75 mg) was administered. Results: The derivatized enantiomers were well separated and detected with good sensitivity. The assay was linear (per enantiomer) at 1–50 μg/L for MDA and 5–250 μg/L for MDMA and MDEA. Analytical recovery, accuracy, repeatability, and intermediate precision data were within required limits. Extraction yields were 82.1%–95.3%. In the study samples, concentrations of R -(−)-MDMA significantly exceeded those of S -(+)-MDMA. Their ratios ( R vs S ) were always >1.0 and increased over time. Concentrations of S -(+)-MDA exceeded those of R -(−)-MDA, their ratios ( R vs S ) also increasing over time but remaining Conclusions: This assay enables sensitive, reliable, and fast enantioselective measurement of MDA, MDMA, and MDEA in small volumes of plasma. The controlled study data confirm previous findings of MDMA and MDA enantiomer ratios ( R vs S ) increasing over time after ingestion of racemic MDMA.
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concentrations and ratios of amphetamine methamphetamine mda MDMA and mdea enantiomers determined in plasma samples from clinical toxicology and driving under the influence of drugs cases by gc nici ms
Journal of Analytical Toxicology, 2003Co-Authors: Frank T Peters, Nele Samyn, Thomas Kraemer, M Wahl, G De Boeck, Hans H MaurerAbstract:Enantiomers of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) exhibit different pharmacological properties. This may be important for the interpretation of analytical results. Plasma samples were analyzed using validated negative ion chemical ionization gas chromatography-mass spectrometry procedures. The results for clinical toxicology cases, divided into screening (SCR) and intoxication (ITX) cases, and those of driving under the influence of drugs (DUID) cases were compared. The concentrations of all enantiomers, except R-(-)-MDA and R-(-)- and S-(+)-MA, in the SCR samples were lower than in ITX and DUID samples. Differences between concentrations in ITX and DUID samples were only significant for both enantiomers of AM (DUID higher). These findings suggested impairment in drugged drivers. Different enantiomer ratios (R vs. S) were found for AM between DUID and SCR samples, for MDMA between ITX and SCR samples, and for MDA between DUID and ITX and DUID and SCR samples. Higher MDMA enantiomer ratios in SCR compared to ITX samples are in accordance with a previously described increase of those ratios over time, possibly allowing differentiation of recent from nonrecent ingestion. Pharmacokinetic analysis of a MDMA poisoning yielded elimination half-lives of 6.0 h for R-(-)-MDMA and 4.1 h for S-(+)-MDMA. The enantiomer ratios rose exponentially over time.
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plasma oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions
Forensic Science International, 2002Co-Authors: Nele Samyn, Caroline T J Lamers, Gert De Boeck, Michelle Wood, Dick De Waard, Karel Brookhuis, Alain Verstraete, W J RiedelAbstract:In a double-blind placebo controlled study on psychomotor skills important for car driving (Study 1), a 75 mg dose of 3,4methylenedioxymethamphetamine (MDMA) was administered orally to 12 healthy Volunteers who were known to be recreational MDMA-users. Toxicokinetic data were gathered by analysis of blood, urine. oral fluid and sweat wipes collected during the first 5 h after administration. Resultant plasma concentrations varied from 21 to 295 ng/ml, with an average peak concentration of 178 ng/ml observed between 2 and 4 h after administration. MDA concentrations never exceeded 20 ng/ml. Corresponding MDMA concentrations in oral fluid, as measured with a specific LC-MS/MS method (which required only 50 mul of oral fluid), generally exceeded those in plasma and peaked at an average concentration of 1215 ng/ml. A substantial intra- and inter-subject variability was observed with this matrix, and values ranged from 50 to 6982 ng/ml MDMA. Somewhat even 4-5 h after ingestion, the MDMA levels in sweat only averaged 25 ng/wipe. In addition to this controlled study, data were collected from 19 MDMA-users who participated in a driving simulator study (Study 2), comparing sober non-drug conditions with MDMA-only and multiple drug use conditions. In this particular study, urine samples were used for general drug screening and oral fluid was collected as an alternative to blood sampling. Analysis of oral fluid samples by LC-MS/MS revealed an average MDMA/MDEA concentration of 1121 ng/ml in the MDMA-only condition, with large inter-subject variability. This was also the case in the multiple drug condition, where generally, significantly higher concentrations of MDMA, MDEA and/or amphetamine were detected in the oral fluid samples. Urine screening revealed the presence of combinations such as MDMA, MDEA, amph, cannabis, cocaine, LSD and psilocine in the rnultiple-drug condition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
Robert Wennig - One of the best experts on this subject based on the ideXlab platform.
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sensitive rapid and validated gas chromatography negative ion chemical ionization mass spectrometry assay including derivatisation with a novel chiral agent for the enantioselective quantification of amphetamine type stimulants in hair
Journal of Chromatography B, 2006Co-Authors: Liliane Ferreira Martins, Heesun Chung, Michel Yegles, Robert WennigAbstract:A novel chiral derivatisation agent, (2S,4R)-N-heptafluorobutyryl-4-heptafluorobutoyloxy-prolyl chloride, was used for the indirect resolution of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) enantiomers using gas chromatography coupled to mass spectrometry operating in the negative-ion chemical ionization mode (GC/MS-NICI). This new chiral derivatisation reagent was readily obtained in optically pure form after a simple two-step synthesis. Optimal derivatisation was accomplished in 15 min at room temperature in a carbonate buffer and the resulting diastereoisomers were base line separated by GC in 12 min only. No racemization was observed during the derivatisation. The method was applied and fully validated for the enantiomeric quantification of amphetamines and methylenedioxylated amphetamines in hair. The analyses of 24 hair specimens from suspected ATS abusers showed that 24 cases were positive for MA and/or AM enantiomers and that in most cases the concentrations of (S)-MA and (S)-AM exceeded those of the corresponding (R)-enantiomers. One hair specimen was tested positive for both enantiomers of MDMA and MDA.
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simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography mass spectrometry
Journal of Chromatography B, 2005Co-Authors: Liliane Ferreira Martins, Heesun Chung, Michel Yegles, Robert WennigAbstract:Abstract Enantioselective quantification of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) enantiomers in hair using gas chromatography–mass spectrometry (GC–MS) is described. Hair specimens were digested with 1 M sodium hydroxide at 100 °C for 30 min and extracted by a solid phase procedure using Cleanscreen ZSDAU020. Extracted analytes were derivatised with ( S )-heptafluorobutyrylprolyl chloride and the resulting diastereoisomers were quantified by GC–MS operating in the negative chemical ionization mode. Extraction yields were between 73.0 and 97.9%. Limits of detection varied in the range of 2.1–45.9 pg/mg hair, whereas the lowest limits of quantification varied between 4.3 and 91.8 pg/mg hair. Intra- and inter-assay precision and respective accuracy were acceptable. The enantiomeric ratios ( R versus S ) of AM, MA, MDA, MDMA and MDEA were determined in hair from suspected amphetamine abusers. Only MA and AM enantiomers were detectable in this collective and the quantification data showed in most cases higher concentrations of ( R )-MA and ( R )-AM than those of the corresponding ( S )-enantiomers.
Thomas Kraemer - One of the best experts on this subject based on the ideXlab platform.
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negative ion chemical ionization gas chromatography mass spectrometry assay for enantioselective measurement of amphetamines in oral fluid application to a controlled study with MDMA and driving under the influence cases
Clinical Chemistry, 2007Co-Authors: Frank T Peters, Nele Samyn, W J Riedel, Thomas Kraemer, Hans H MaurerAbstract:Background: Enantioselective analysis of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) helps interpret toxicological results. Methods have been described for various matrices, but so far not for oral fluid, a matrix of increasing importance in testing for drugs of abuse, especially in the context of driving under the influence of drugs (DUID). Methods: After dilution with 200 μL carbonate buffer (pH 9), oral fluid samples (10–50 μL) were derivatized with S -heptafluorobutyrylprolyl chloride. The resulting diastereomers were extracted into 100 μL of cyclohexane, separated by gas chromatography (HP-5MS column), and detected by mass spectrometry in the negative-ion chemical ionization mode (GC-NICI-MS). The method was validated and applied to samples from a controlled study with MDMA and from authentic DUID cases. Results: The derivatized AM, MA, MDA, MDMA, and MDEA enantiomers were well separated from each other. The method was linear from 5–250 μg/L per enantiomer of MDA and from 25–1250 μg/L per enantiomer of AM, MA, MDMA, and MDEA. With the exception of MDEA, analytical recoveries, repeatability, and intermediate precision were within required limits. The analyte concentrations and enantiomer ratios in the application samples correlated only weakly with corresponding published plasma data. Conclusions: This sensitive, reliable, and fast GC-NICI-MS assay enantioselectively measures AM, MA, MDA, and MDMA in oral fluid samples. Prediction of plasma concentrations and enantiomer ratios from respective oral fluid data is not possible.
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drug testing in blood validated negative ion chemical ionization gas chromatographic mass spectrometric assay for enantioselective measurement of the designer drugs mdea MDMA and mda and its application to samples from a controlled study with MDMA
Clinical Chemistry, 2005Co-Authors: Frank T Peters, Nele Samyn, Caroline T J Lamers, W J Riedel, Thomas Kraemer, Gert De Boeck, Hans H MaurerAbstract:Background: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA. Methods: The analytes were extracted from ≤0.2 mL of plasma by mixed-mode solid-phase extraction. After derivatization with S -(−)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in the negative-ion chemical ionization mode. The method was fully validated and applied to samples from a controlled study in which a single dose of racemic MDMA (75 mg) was administered. Results: The derivatized enantiomers were well separated and detected with good sensitivity. The assay was linear (per enantiomer) at 1–50 μg/L for MDA and 5–250 μg/L for MDMA and MDEA. Analytical recovery, accuracy, repeatability, and intermediate precision data were within required limits. Extraction yields were 82.1%–95.3%. In the study samples, concentrations of R -(−)-MDMA significantly exceeded those of S -(+)-MDMA. Their ratios ( R vs S ) were always >1.0 and increased over time. Concentrations of S -(+)-MDA exceeded those of R -(−)-MDA, their ratios ( R vs S ) also increasing over time but remaining Conclusions: This assay enables sensitive, reliable, and fast enantioselective measurement of MDA, MDMA, and MDEA in small volumes of plasma. The controlled study data confirm previous findings of MDMA and MDA enantiomer ratios ( R vs S ) increasing over time after ingestion of racemic MDMA.
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concentrations and ratios of amphetamine methamphetamine mda MDMA and mdea enantiomers determined in plasma samples from clinical toxicology and driving under the influence of drugs cases by gc nici ms
Journal of Analytical Toxicology, 2003Co-Authors: Frank T Peters, Nele Samyn, Thomas Kraemer, M Wahl, G De Boeck, Hans H MaurerAbstract:Enantiomers of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) exhibit different pharmacological properties. This may be important for the interpretation of analytical results. Plasma samples were analyzed using validated negative ion chemical ionization gas chromatography-mass spectrometry procedures. The results for clinical toxicology cases, divided into screening (SCR) and intoxication (ITX) cases, and those of driving under the influence of drugs (DUID) cases were compared. The concentrations of all enantiomers, except R-(-)-MDA and R-(-)- and S-(+)-MA, in the SCR samples were lower than in ITX and DUID samples. Differences between concentrations in ITX and DUID samples were only significant for both enantiomers of AM (DUID higher). These findings suggested impairment in drugged drivers. Different enantiomer ratios (R vs. S) were found for AM between DUID and SCR samples, for MDMA between ITX and SCR samples, and for MDA between DUID and ITX and DUID and SCR samples. Higher MDMA enantiomer ratios in SCR compared to ITX samples are in accordance with a previously described increase of those ratios over time, possibly allowing differentiation of recent from nonrecent ingestion. Pharmacokinetic analysis of a MDMA poisoning yielded elimination half-lives of 6.0 h for R-(-)-MDMA and 4.1 h for S-(+)-MDMA. The enantiomer ratios rose exponentially over time.