Drug Testing and Analysis

Cover image for Vol. 4 Issue 12

Special Issue: Stable isotope ratio analysis in sports anti-doping

December 2012

Volume 4, Issue 12

Pages 891–1039

Issue edited by: Adam Cawley

  1. Editorial

    1. Top of page
    2. Editorial
    3. Perspectives
    4. Reviews
    5. Research articles
    6. Perspectives
    7. Research articles
  2. Perspectives

    1. Top of page
    2. Editorial
    3. Perspectives
    4. Reviews
    5. Research articles
    6. Perspectives
    7. Research articles
    1. Isotope ratio mass spectrometry – history and terminology in brief (pages 893–896)

      Ulrich Flenker

      Article first published online: 12 SEP 2012 | DOI: 10.1002/dta.1399

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      Isotope ratio mass spectrometry is a rather traditional methodology which dates back to the nineteen-thirties. Most of the recent developments come from the introduction of so-called continuous flow interfaces. Mostly due to the relative nature of stable isotope analytical data, a specific terminology has emerged. In respect to stable isotope analysis in doping control, proposals are made concerning a more consistent and precise terminology of steroids.

  3. Reviews

    1. Top of page
    2. Editorial
    3. Perspectives
    4. Reviews
    5. Research articles
    6. Perspectives
    7. Research articles
    1. Complementary stable carbon isotope ratio and amount of substance measurements in sports anti-doping (pages 897–911)

      Adam T. Cawley and Adrian V. George

      Article first published online: 13 JUL 2012 | DOI: 10.1002/dta.1378

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      Markers of synthetically derived steroids are reviewed on the basis of abnormal urinary excretions and low 13C content. A combinatorial approach is presented for the interpretation of GC/LC-MS and GC-C-IRMS data in the anti-doping context. This methodology can allow all relevant information concerning an individual's metabolism to be assessed in order to make an informed decision with respect to a doping violation.

    2. Calibration and data processing in gas chromatography combustion isotope ratio mass spectrometry (pages 912–922)

      Ying Zhang, Herbert J. Tobias, Gavin L. Sacks and J. Thomas Brenna

      Article first published online: 24 FEB 2012 | DOI: 10.1002/dta.394

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      GCC-IRMS data must be converted from a stream of continuously changing raw ion current data to isotope ratios with a precision of about SD(δ13C) = 0.3 ‰ , corresponding to precision for absolute 13C/12C with RSD = 0.03%. Chromatographically well-resolved peaks are much preferred for summation, the usual method of integration. Several methods of calibration are described and contrasted.

  4. Research articles

    1. Top of page
    2. Editorial
    3. Perspectives
    4. Reviews
    5. Research articles
    6. Perspectives
    7. Research articles
    1. Examination of the kinetic isotopic effect to the acetylation derivatization for the gas chromatographic-combustion-isotope ratio mass spectrometric doping control analysis of endogenous steroids (pages 923–927)

      Yiannis S. Angelis, Maroula K. Kioussi, Polyxeni Kiousi, J. Thomas Brenna and Costas G. Georgakopoulos

      Article first published online: 28 FEB 2012 | DOI: 10.1002/dta.408

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      In Gas Chromatographic-Combustion-Isotope Ratio Mass Spectrometry (GC/C/IRMS) analysis, endogenous androgenic anabolic steroids are commonly acetylated using acetic anhydride reagent. Variability in kinetic isotope effects (KIE) due to steroid structures could cause fractionation of endogenous steroid carbon. To test for possible KIE influence on δ13C, acetic anhydride of graded isotope ratio within the natural abundance range was used under normal derivatization conditions to test for linearity. We conclude that δ13C calculated from the mass balance equation is independent of the δ13C of the acetic anhydride reagent, and that net KIE under normal derivatization conditions do not bias the final reported steroid δ13C.

    2. Certification of steroid carbon isotope ratios in a freeze-dried human urine reference material (pages 928–933)

      Ellaine Munton, Fong-Ha Liu, E. John Murby and D. Brynn Hibbert

      Article first published online: 29 APR 2012 | DOI: 10.1002/dta.1366

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      Describes the certification of the carbon isotope ratios of testosterone, two testosterone metabolites, and endogenous reference compounds, in a freeze dried human urine reference material. Measurement procedure and estimation of measurement uncertainty are described.

  5. Perspectives

    1. Top of page
    2. Editorial
    3. Perspectives
    4. Reviews
    5. Research articles
    6. Perspectives
    7. Research articles
    1. Validity of stable isotope data in doping control: perspectives and proposals (pages 934–941)

      Ulrich Flenker, Leo N. Geppert and Katja Ickstadt

      Article first published online: 12 SEP 2012 | DOI: 10.1002/dta.1398

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      We propose using Bayesian mixture models for 13C/12C analysis of endogenous urinary steroids. The validity of a given result depends on both the analytical uncertainty and the prior probability of doping offenses. Low analytical uncertainties but high prior probabilities facilitate valid detection of doping offenses. For that reason, initial suspicions should be well-substantiated before conducting 13C/12C analysis. Additionally, information about relevant 13C/12C distributions – including both steroid users and non-users – is needed.

  6. Research articles

    1. Top of page
    2. Editorial
    3. Perspectives
    4. Reviews
    5. Research articles
    6. Perspectives
    7. Research articles
    1. Investigations on carbon isotope ratios and concentrations of urinary formestane (pages 942–950)

      Thomas Piper, Gregor Fusshöller, Caroline Emery, Wilhelm Schänzer and Martial Saugy

      Article first published online: 22 FEB 2012 | DOI: 10.1002/dta.386

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      The aromatase inhibitor formestane (4-hydroxy-androst-4-ene-3,17-dione, F) is prohibited in sports by the World Anti-Doping Agency. A method to determine the carbon isotope ratio (CIR) of F in urine samples was developed and validated. Routine samples (n = 42) showing concentrations of F above 5 ng/mL were investigated and enabled elucidation of CIR of endogenous F and subsequent the calculation of a reference limit to be 2.9 ‰ for the difference between pregnanediol and F.

    2. Carbon isotope ratio analysis of endogenous glucocorticoid urinary metabolites after cortisone acetate and adrenosterone administration for doping control (pages 951–961)

      Lance Brooker, Adam Cawley, Ray Kazlauskas, Catrin Goebel and Adrian George

      Article first published online: 17 SEP 2012 | DOI: 10.1002/dta.1403

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      Glucocorticoids are listed on the World Anti-Doping Agency Prohibited List. The detection of hydrocortisone or cortisone administration is complicated because the human body also produces these steroids naturally. However, isotope ratio analysis of endogenous glucocorticoid urinary metabolites can be used to confirm abuse. In this work we confirm the suitability of GC-C-IRMS for this purpose and demonstrate how cortisone and adrenosterone administration can be differentiated.

    3. Two-dimensional gas chromatography with heart-cutting for isotope ratio mass spectrometry analysis of steroids in doping control (pages 962–969)

      A. D. Brailsford, I. Gavrilović, R. J. Ansell, D. A. Cowan and A. T. Kicman

      Article first published online: 3 JUL 2012 | DOI: 10.1002/dta.1379

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      Two-dimensional GC (GC-GC) with heart-cutting is investigated as an approach to simplify sample purification for the IRMS analysis of underivatised urinary steroids. A cyanopropyl/phenyl column was used in the GC1 to optimise steroid separation, before a phenyl-methylpolysiloxane column focused analytes into narrower peaks prior to MS analysis. In addition, eluent from GC2 was split, with> 80 % flowing to the IRMS and the remainder entering a scanning MS facilitating peak identification.

    4. Determination of 6-mercaptopurine in the presence of uric acid using modified multiwall carbon nanotubes-TiO2 as a voltammetric sensor (pages 970–977)

      Ali A. Ensafi and H. Karimi-Maleh

      Article first published online: 3 MAY 2011 | DOI: 10.1002/dta.286

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      A modified electrode (prepared by incorporating TiO2 nanoparticles with p-aminophenol as a mediator) was used as voltammetric sensor for the determination of 6-mercaptopurine and in the presence of uric acid. The voltammograms of 6–mercaptopurine and uric acid in a mixture can be separated from each other by differential pulse voltammetry with a potential difference of 380 mV. The method was successfully applied for the determination of 6–mercaptopurine and uric acid in drug and urine samples.

    5. Voltammetric determination of glutathione in haemolysed erythrocyte and tablet samples using modified-multiwall carbon nanotubes paste electrode (pages 978–985)

      Ali A. Ensafi, Samira Dadkhah-Tehrani and Hassan Karimi-Maleh

      Article first published online: 1 OCT 2011 | DOI: 10.1002/dta.347

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      Reduced glutathione, the most abundant non-protein thiol, plays numerous important roles in transport, catabolism, protein and DNA synthesis, transport, catabolism and metabolism. Glutathione can protect the cell against toxicity, hypoxia, or mutagenicty, and many carcinogens.

    6. 1,3-Dimethylamylamine (DMAA) in supplements and geranium products: natural or synthetic? (pages 986–990)

      Ying Zhang, Ross M. Woods, Zachary S. Breitbach and Daniel W. Armstrong

      Article first published online: 12 JUL 2012 | DOI: 10.1002/dta.1368

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      1,3-Dimethylamylamine (DMAA) is not a single compound but rather a mixture of four stereoisomers. When produced synthetically, DMAA is a mixture of two racemates and has a distinct diastereomeric ratio. The stereoisomeric ratios of the DMAA in supplements and synthetic DMAA were indistinguishable. DMAA was either not found in natural geranium extracts or in two cases, at trace levels with a different stereoisomeric composition.

    7. Spectophotometric methods for determination of cefdinir in pharmaceutical formulations via derivatization with 1,2-naphthoquinone-4-sulfonate and 4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole (pages 991–1000)

      Ayman A. Gouda, Hisham Hashem and Wafaa Hassan

      Article first published online: 28 APR 2011 | DOI: 10.1002/dta.280

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      Two new simple, sensitive, accurate and precise spectrophotometric methods have been developed and validated for the determination of cefdinir (CFD) in bulk drug and in its pharmaceutical formulations with 1, 2-napthaquinone-4-sulfonic acid sodium (NQS) or 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl).

    8. Rapid enantiomeric separation and simultaneous determination of phenethylamines by ultra high performance liquid chromatography with fluorescence and mass spectrometric detection: application to the analysis of illicit drugs distributed in the Japanese market and biological samples (pages 1001–1008)

      Shinsuke Inagaki, Haruo Hirashima, Sayuri Taniguchi, Tatsuya Higashi, Jun Zhe Min, Ruri Kikura-Hanajiri, Yukihiro Goda and Toshimasa Toyo'oka

      Article first published online: 8 MAR 2012 | DOI: 10.1002/dta.1327

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      A rapid enantiomeric separation and simultaneous determination method based on ultra high-performance liquid chromatography (UHPLC) was developed for phenethylamine-type abused drugs using (R)-(-)-DBD-Py-NCS as the chiral derivatization reagent. The developed method was successfully applied to the analysis of hair specimens from rats that were dosed with diphenyl(pyrrolidin-2-yl)methanol (D2PM). (R)- and (S)-D2PM from rat hair specimens were enantiomerically separated and detected high sensitivity using UHPLC-fluorescence detection.

    9. Novel screen-printed electrode for the determination of dodecyltrimethylammonium bromide in water samples (pages 1009–1013)

      Gehad G. Mohamed, Tamer Awad Ali, M. F. El-Shahat, M. A. Migahed and A. M. Al-Sabagh

      Article first published online: 13 OCT 2011 | DOI: 10.1002/dta.366

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      The construction and electrochemical response of a screen-printed electrode for the determination of dodecyltrimethylammonium bromide (DTAB) are described. DTA-TPB ion association complex was used as an electroactive material with DOS as a solvent mediator. The sensor displayed a stable response for 6 months, concentration range 1.20 × 10-2-5.6 × 10-7 mol L-1 at 25 °C with Nernstian slope of 55.95 ± 0.58 mV decade-1 and detection limit of 6 × 10-7 mol L-1. The sensor was used for the determination of DTAB in water samples.

    10. Flexibility and applicability of β-expectation tolerance interval approach to assess the fitness of purpose of pharmaceutical analytical methods (pages 1014–1027)

      A. Bouabidi, M. Talbi, H. Bourichi, A. Bouklouze, M. El Karbane, B. Boulanger, Y. Brik, Ph. Hubert and E. Rozet

      Article first published online: 21 MAY 2012 | DOI: 10.1002/dta.1345

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      In this work, the accuracy profile approach used for method validation is evaluated on several types of analytical methods encountered in the pharmaceutical industrial field and also covering different pharmaceutical matrices. The four studied examples depicted the versatility of this approach for matrices ranging from tablets to syrups, different techniques such as liquid chromatography, or UV spectrophotometry and for different categories of assays encountered in the pharmaceutical industry i.e. content assays, dissolution assays, and quantitative impurity assays.

    11. Interconversion of ephedrine and pseudoephedrine during chemical derivatization (pages 1028–1033)

      Colton H. F. Wong, Emmie N. M. Ho, W. H. Kwok, David K. K. Leung, Gary N. W. Leung, Francis P. W. Tang, April S. Y. Wong, Jenny K. Y. Wong, Nola H. Yu and Terence S. M. Wan

      Article first published online: 26 JUN 2012 | DOI: 10.1002/dta.1384

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      Diastereoisomeric interconversion between ephedrine and pseudoephedrine was observed after derivatisation with fluorinated acylating agents (e.g. heptafluorobutyric anhydride, pentafluoropropionic anhydride and trifluoroacetic anhydride). The extent of conversion appeared to increase with the degree of fluorination of the acylating agent, and a mechanism of the interconversion was proposed. These findings show that fluorinated acylating agents should not be used for the unequivocal identification or quantification of ephedrine and pseudoephedrine as the results obtained can be erroneous.

    12. Application of multiwalled carbon nanotubes/ionic liquid modified electrode for amperometric determination of sulfadiazine (pages 1034–1039)

      Xiaoping Hong, Yan Zhu and Jingying Ma

      Article first published online: 26 SEP 2011 | DOI: 10.1002/dta.329

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      N-octyl-pyridinium-hexafluorophosphate ionic liquid was used as the matrix for fabricating a MWCNTs/OPPF6 GC electrode. Compared to bare GC electrode, the new modified electrode generated a greatly improved electrochemical detection of sulfadiazine, including low oxidation over potential, high current responses, and good anti fouling performance.

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