Universität zu Köln

Rydevik, Axel, Bondesson, Ulf, Thevis, Mario and Hedeland, Mikael ORCID: 0000-0001-8962-2815 (2013). Mass spectrometric characterization of glucuronides formed by a new concept, combining Cunninghamella elegans with TEMPO. J. Pharm. Biomed. Anal., 84. S. 278 - 285. AMSTERDAM: ELSEVIER. ISSN 1873-264X

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Abstract

A new concept for the production of drug glucuronides is presented and the products formed were characterized using ultra high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Glucuronic acid conjugates are important phase II metabolites of a wide range of drugs. There is a lack of commercially available glucuronides and classic synthetic methods are tedious and expensive. Thus, new methods of glucuronide synthesis are needed. Selective androgen receptor modulators (SARMs) of the aryl propionamide class were used as model compounds and were incubated with the fungus Cunninghamella elegans which was previously known to conjugate drugs with glucose. The resulting glucoside metabolites were then oxidized with tetramethylpiperidinyl-1-oxy (TEMPO). UPLC-HRMS analysis showed that the peaks corresponding to the glucosides had disappeared after the reaction and were replaced by peaks with m/z consistent with the corresponding glucuronic acid conjugates. The MS/MS spectra of the reaction products were investigated and the observed fragment ion pattern corroborated the suggested structural change. A comparison in terms of retention times and product ion spectra between the glucuronides formed by the new method and those produced by liver microsomes indicated that the conjugates from the two different sources were identical, thus demonstrating the human relevance of the presented technique. Furthermore, the glucuronides formed by the presented method were readily hydrolyzed by beta-glucuronidase which further gave evidence as to the fact that they were of beta configuration. The investigated method was easy to perform, required a low input of work and had a low cost. (C) 2013 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rydevik, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Bondesson, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedeland, Mikael UNSPECIFIED orcid.org/0000-0001-8962-2815 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-475609
DOI:	10.1016/j.jpba.2013.06.012
Journal or Publication Title:	J. Pharm. Biomed. Anal.
Volume:	84
Page Range:	S. 278 - 285
Date:	2013
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1873-264X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANDROGEN RECEPTOR MODULATORS; FUNGAL METABOLISM; II METABOLITES; PHASE-I; BIOTRANSFORMATION; ELUCIDATION Multiple languages Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47560