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1.
Molecules ; 29(2)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38257243

ABSTRACT

The misuse of growth-promoting drugs such as beta-2 agonists and steroids is a known problem in farming and sports competitions. Prior to the analysis of biological samples via liquid chromatography (LC)-mass spectrometry (MS) or gas chromatography (GC)-MS, sufficient sample preparation is required to reliably identify or determine the residues of drugs. In practice, broad screening methods are often used to save time and analyze as many compounds as possible. This review was conceptualized to analyze the literature from 2018 until October 2023 for sample preparation procedures applied to animal specimens before LC- or GC-MS analysis. The animals were either used in farming or sports. In the present review, solid phase extraction (SPE) was observed as the dominant sample clean-up technique for beta-2 agonists and steroids, followed by protein precipitation. For the extraction of beta-2 agonists, mixed-mode cation exchanger-based SPE phases were preferably applied, while for the steroids, various types of SPE materials were reported. Furthermore, dispersive SPE-based QuEChERs were utilized. Combinatory use of SPE and liquid-liquid extraction (LLE) was observed to cover further drug classes in addition to beta-2 agonists in broader screening methods.


Subject(s)
Agriculture , Anesthetics, Local , Animals , Farms , Antacids , Intercellular Signaling Peptides and Proteins , Mammals , Steroids
2.
Molecules ; 28(20)2023 Oct 21.
Article in English | MEDLINE | ID: mdl-37894685

ABSTRACT

The aim of this study was to develop and optimize a chiral HPLC-MS/MS method for quantitative analysis of (R)-/(S)-salbutamol and (R)-/(S)-salbutamol-4'-O-sulfate in human urine to allow for bioanalytical quantitation of the targeted analytes and investigations of stereoselectivity in the sulfonation pathway of human phase Ⅱ metabolism. For analytical method development, a systematic screening of columns and mobile phases to develop a separation via enantiomerically selective high performance liquid chromatography was performed. Electrospray ionization settings were optimized via multiple-step screening and a full factorial design-of-experiment. Both approaches were performed matrix-assisted and the predicted values were compared. The full factorial design was superior in terms of prediction power and knowledge generation. Performing a longitudinal excretion study in one healthy volunteer allowed for the calculation of excretion rates for all four targeted analytes. For this proof-of-concept, either racemic salbutamol or enantiopure levosalbutamol was administered perorally or via inhalation, respectively. A strong preference for sulfonation of (R)-salbutamol for inhalation and peroral application was found in in vivo experiments. In previous studies phenol sulfotransferase 1A3 was described to be mainly responsible for salbutamol sulfonation in humans. Thus, in vitro and in silico investigations of the stereoselectivity of sulfotransferase 1A3 complemented the study and confirmed these findings.


Subject(s)
Albuterol , Tandem Mass Spectrometry , Humans , Albuterol/analysis , Albuterol/chemistry , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Levalbuterol , Administration, Inhalation , Stereoisomerism
3.
Front Mol Biosci ; 9: 827638, 2022.
Article in English | MEDLINE | ID: mdl-35281274

ABSTRACT

For in vitro investigations on human sulfotransferase (SULT) catalyzed phase II metabolism, the costly cofactor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) is generally needed. In the present study, we developed and optimized a new approach that combines SULT-dependent biotransformation using recombinant and permeabilized fission yeast cells (enzyme bags) with PAPS production in situ applying quality by design principles. In the initial application of the procedure, yeast cells expressing human SULT1A3 were used for the production of 4'-hydroxypropranolol-4-O-sulfate from 4-hydroxypropranolol. The optimized protocol was then successfully transferred to other sulfonation reactions catalyzed by SULT2A1, SULT1E1, or SULT1B1. The concomitant degradation of some sulfoconjugates was investigated, and further optimization of the reaction conditions was performed in order to reduce product loss. Also, the production of stable isotope labelled sulfoconjugates was demonstrated utilizing isotopically labelled substrates or 34S-sulfate. Overall, this new approach results in higher space-time yields while at the same time reducing experimental cost.

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