Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis
Detailed structural information on metabolites serving as target analytes in clinical, forensic, and sports drug testing programmes is of paramount importance to ensure unequivocal test results. In the present study, the utility of collision cross section (CCS) analysis by travelling wave ion mobili...
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ftubkoeln:oai:USBKOELN.ub.uni-koeln.de:38766 2023-05-15T17:53:57+02:00 Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis Thevis, Mario Dib, Josef Thomas, Andreas Hoeppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schaenzer, Wilhelm 2015 https://kups.ub.uni-koeln.de/38766/ eng eng WILEY Thevis, Mario, Dib, Josef, Thomas, Andreas orcid:0000-0003-1199-0743 , Hoeppner, Sebastian, Lagojda, Andreas, Kuehne, Dirk, Sander, Mark, Opfermann, Georg and Schaenzer, Wilhelm (2015). Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis. Drug Test. Anal., 7 (11-12). S. 1050 - 1057. HOBOKEN: WILEY. ISSN 1942-7611 ddc:no doc-type:article publishedVersion 2015 ftubkoeln 2022-11-09T07:26:00Z Detailed structural information on metabolites serving as target analytes in clinical, forensic, and sports drug testing programmes is of paramount importance to ensure unequivocal test results. In the present study, the utility of collision cross section (CCS) analysis by travelling wave ion mobility measurements to support drug metabolite characterization efforts was tested concerning recently identified glucuronic acid conjugates of the anabolic-androgenic steroid stanozolol. Employing travelling-wave ion mobility spectrometry/quadrupole-time-of-flight mass spectrometry, drift times of five synthetically derived and fully characterized steroid glucuronides were measured and subsequently correlated to respective CCSs as obtained in silico to form an analyte-tailored calibration curve. The CCSs were calculated by equilibrium structure minimization (density functional theory) using the programmes ORCA with the data set B3LYP/6-31G and MOBCAL utilizing the trajectory method (TM) with nitrogen as drift gas. Under identical experimental conditions, synthesized and/or urinary stanozolol-N and O-glucuronides were analyzed to provide complementary information on the location of glucuronidation. Finally, the obtained data were compared to CCS results generated by the system's internal algorithm based on a calibration employing a polyalanine analyte mixture. The CCSs Omega(N2) calculated for the five steroid glucuronide calibrants were found between 180 and 208 angstrom(2), thus largely covering the observed and computed CCSs for stanozolol-N1'-, stanozolol-N2'-, and stanozolol-O-glucuronide found at values between 195.1 and 212.4 angstrom(2). The obtained data corroborated the earlier suggested N- and O-glucuronidation of stanozolol, and demonstrate the exploit of ion mobility and CCS computation in structure characterization of phase-II metabolic products; however, despite reproducibly measurable differences in ion mobility of stanozolol-N1'-, N2'-, and O-glucuronides, the discriminatory power of the chosen CCS ... Article in Journal/Newspaper Orca Cologne University: KUPS |
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English |
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ddc:no Thevis, Mario Dib, Josef Thomas, Andreas Hoeppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schaenzer, Wilhelm Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
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ddc:no |
description |
Detailed structural information on metabolites serving as target analytes in clinical, forensic, and sports drug testing programmes is of paramount importance to ensure unequivocal test results. In the present study, the utility of collision cross section (CCS) analysis by travelling wave ion mobility measurements to support drug metabolite characterization efforts was tested concerning recently identified glucuronic acid conjugates of the anabolic-androgenic steroid stanozolol. Employing travelling-wave ion mobility spectrometry/quadrupole-time-of-flight mass spectrometry, drift times of five synthetically derived and fully characterized steroid glucuronides were measured and subsequently correlated to respective CCSs as obtained in silico to form an analyte-tailored calibration curve. The CCSs were calculated by equilibrium structure minimization (density functional theory) using the programmes ORCA with the data set B3LYP/6-31G and MOBCAL utilizing the trajectory method (TM) with nitrogen as drift gas. Under identical experimental conditions, synthesized and/or urinary stanozolol-N and O-glucuronides were analyzed to provide complementary information on the location of glucuronidation. Finally, the obtained data were compared to CCS results generated by the system's internal algorithm based on a calibration employing a polyalanine analyte mixture. The CCSs Omega(N2) calculated for the five steroid glucuronide calibrants were found between 180 and 208 angstrom(2), thus largely covering the observed and computed CCSs for stanozolol-N1'-, stanozolol-N2'-, and stanozolol-O-glucuronide found at values between 195.1 and 212.4 angstrom(2). The obtained data corroborated the earlier suggested N- and O-glucuronidation of stanozolol, and demonstrate the exploit of ion mobility and CCS computation in structure characterization of phase-II metabolic products; however, despite reproducibly measurable differences in ion mobility of stanozolol-N1'-, N2'-, and O-glucuronides, the discriminatory power of the chosen CCS ... |
format |
Article in Journal/Newspaper |
author |
Thevis, Mario Dib, Josef Thomas, Andreas Hoeppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schaenzer, Wilhelm |
author_facet |
Thevis, Mario Dib, Josef Thomas, Andreas Hoeppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schaenzer, Wilhelm |
author_sort |
Thevis, Mario |
title |
Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
title_short |
Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
title_full |
Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
title_fullStr |
Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
title_full_unstemmed |
Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
title_sort |
complementing the characterization of in vivo generated n-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
publisher |
WILEY |
publishDate |
2015 |
url |
https://kups.ub.uni-koeln.de/38766/ |
genre |
Orca |
genre_facet |
Orca |
op_relation |
Thevis, Mario, Dib, Josef, Thomas, Andreas orcid:0000-0003-1199-0743 , Hoeppner, Sebastian, Lagojda, Andreas, Kuehne, Dirk, Sander, Mark, Opfermann, Georg and Schaenzer, Wilhelm (2015). Complementing the characterization of in vivo generated N-glucuronic acid conjugates of stanozolol by collision cross section computation and analysis. Drug Test. Anal., 7 (11-12). S. 1050 - 1057. HOBOKEN: WILEY. ISSN 1942-7611 |
_version_ |
1766161660247015424 |