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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crwiley:10.1002/dta.1907 2024-06-02T08:12:49+00:00 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 Höppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schänzer, Wilhelm 2015 http://dx.doi.org/10.1002/dta.1907 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fdta.1907 http://onlinelibrary.wiley.com/wol1/doi/10.1002/dta.1907/fullpdf en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Drug Testing and Analysis volume 7, issue 11-12, page 1050-1056 ISSN 1942-7603 1942-7611 journal-article 2015 crwiley https://doi.org/10.1002/dta.1907 2024-05-03T11:12:34Z 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 Ω N2 calculated for the five steroid glucuronide calibrants were found between 180 and 208 Å 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 Å 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‐ N 1'‐, N 2'‐, and O ‐glucuronides, the discriminatory power of the chosen CCS computation ... Article in Journal/Newspaper Orca Wiley Online Library Drug Testing and Analysis 7 11-12 1050 1056 |
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Wiley Online Library |
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crwiley |
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English |
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 Ω N2 calculated for the five steroid glucuronide calibrants were found between 180 and 208 Å 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 Å 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‐ N 1'‐, N 2'‐, and O ‐glucuronides, the discriminatory power of the chosen CCS computation ... |
format |
Article in Journal/Newspaper |
author |
Thevis, Mario Dib, Josef Thomas, Andreas Höppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schänzer, Wilhelm |
spellingShingle |
Thevis, Mario Dib, Josef Thomas, Andreas Höppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schänzer, Wilhelm Complementing the characterization of in vivo generated N‐glucuronic acid conjugates of stanozolol by collision cross section computation and analysis |
author_facet |
Thevis, Mario Dib, Josef Thomas, Andreas Höppner, Sebastian Lagojda, Andreas Kuehne, Dirk Sander, Mark Opfermann, Georg Schänzer, 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 |
http://dx.doi.org/10.1002/dta.1907 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fdta.1907 http://onlinelibrary.wiley.com/wol1/doi/10.1002/dta.1907/fullpdf |
genre |
Orca |
genre_facet |
Orca |
op_source |
Drug Testing and Analysis volume 7, issue 11-12, page 1050-1056 ISSN 1942-7603 1942-7611 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/dta.1907 |
container_title |
Drug Testing and Analysis |
container_volume |
7 |
container_issue |
11-12 |
container_start_page |
1050 |
op_container_end_page |
1056 |
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1800759373785464832 |