کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1220826 1494621 2015 21 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Liquid chromatography-quadrupole time-of-flight mass spectrometry for screening in vitro drug metabolites in humans: investigation on seven phenethylamine-based designer drugs
ترجمه فارسی عنوان
طیف سنجی جرمی کروماتوگرافی مایع و چهاربعدی برای غربالگری متابولیت های درون آزمایشگاهی در انسان: تحقیق بر روی هفت داروهای طراح مبتنی بر فنیل اتیلامین
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی


• Human in vitro metabolism of seven phenethylamine-based designer drugs was studied.
• Stepwise in vitro experimental design was described to enhance data robustness.
• Potential in vitro metabolites were screened by non-target analysis of LC-QTOF-MS.
• Limited numbers of metabolites were found similar to other phenethylamine-based drugs.
• In vitro metabolism of most of the targeted drugs progressed at slow paces.

Phenethylamine-based designer drugs are prevalent within the new psychoactive substance market. Characterisation of their metabolites is important in order to identify suitable biomarkers which can be used for better monitoring their consumption. Careful design of in vitro metabolism experiments using subcellular liver fractions will assist in obtaining reliable outcomes for such purposes. The objective of this study was to stepwise investigate the in vitro human metabolism of seven phenethylamine-based designer drugs using individual families of enzymes. This included para-methoxyamphetamine, para-methoxymethamphetamine, 4-methylthioamphetamine, N-methyl-benzodioxolylbutanamine, benzodioxolylbutanamine, 5-(2-aminopropyl) benzofuran and 6-(2-aminopropyl) benzofuran. Identification and structural elucidation of the metabolites was performed using liquid chromatography-quadrupole-time-of-flight mass spectrometry. The targeted drugs were mainly metabolised by cytochrome P450 enzymes via O-dealkylation as the major pathway, followed by N-dealkylation, oxidation of unsubstituted C atoms and deamination (to a small extent). These drugs were largely free from Phase II metabolism. Only a limited number of metabolites were found which was consistent with the existing literature for other phenethylamine-based drugs. Also, the metabolism of most of the targeted drugs progressed at slow rate. The reproducibility of the identified metabolites was assessed through examining formation patterns using different incubation times, substrate and enzyme concentrations. Completion of the work has led to a set of metabolites which are representative for specific detection of these drugs in intoxicated individuals and also for meaningful evaluation of their use in communities by wastewater-based drug epidemiology.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 114, 10 October 2015, Pages 355–375
نویسندگان
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