LC-MS/MS detection of unaltered glucuronoconjugated metabolites of metandienone
| Autor: | Cristina Gómez, Aristotelis Kotronoulas, Georgina Balcells, Lorena Garrostas, Jesús Joglar, Oscar J. Pozo, Rosa Ventura, Argitxu Esquivel |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chromatography Metabolite 010401 analytical chemistry Selected reaction monitoring Metandienone Pharmaceutical Science Urine Mass spectrometry Tandem mass spectrometry 01 natural sciences 0104 chemical sciences Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Enzymatic hydrolysis medicine Environmental Chemistry Glucuronide Spectroscopy medicine.drug |
| Zdroj: | Drug Testing and Analysis. 9:534-544 |
| ISSN: | 1942-7603 |
| Popis: | The aim of this study was to evaluate the direct detection of glucuronoconjugated metabolites of metandienone (MTD) and their detection times. Metabolites resistant to enzymatic hydrolysis were also evaluated. Based on the common mass spectrometric behaviour of steroid glucuronides, three liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategies were applied for the detection of unpredicted and predicted metabolites: precursor ion scan (PI), neutral loss scan (NL), and theoretical selected reaction monitoring (SRM) methods. Samples from four excretion studies of MTD were analyzed for both the detection of metabolites and the establishment of their detection times. Using PI and NL methods, seven metabolites were observed in post-administration samples. SRM methods allowed for the detection of 13 glucuronide metabolites. The detection times, measured by analysis with an SRM method, were between 1 and 22 days. The metabolite detected for the longest time was 18-nor-17β-hydroxymethyl-17α-methyl-5β-androsta-1,4,13-triene-3-one-17-glucuronide. One metabolite was resistant to hydrolysis with β-glucuronidase; however it was only detected in urine up to four days after administration. The three glucuronide metabolites with the highest retrospectivity were identified by chemical synthesis or mass spectrometric data, and although they were previously reported, this is the first time that analytical data of the intact phase II metabolites are presented for some of them. The LC-MS/MS strategies applied have demonstrated to be useful for detecting glucuronoconjugated metabolites of MTD, including glucuronides resistant to enzymatic hydrolysis which cannot be detected by conventional approaches. Copyright © 2016 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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