کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1198974 1493492 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting tryptophan and tyrosine metabolism by liquid chromatography tandem mass spectrometry
ترجمه فارسی عنوان
هدف قرار دادن متابولیسم تریپتوفان و تیروزین توسط کروماتوگرافی مایع اسپکترومتری دو طرفه
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی


• An LC–MS/MS method for the study of tryptophan and tyrosine metabolism is presented.
• Concurrent quantification of 4 competitive large neutral amino acids is offered.
• Fully validated in human serum and urine, and in mice prefrontal cortex extracts.
• Urinary concentrations for 18 analytes in 13 healthy individuals were calculated.
• Applicability proved by analyzing samples from a family with the Brunner syndrome.

An imbalance in tryptophan (Trp) and tyrosine (Tyr) metabolites is associated with neurological and inflammatory disorders. The accurate and precise measurement of these compounds in biological specimens is a powerful tool to understand the biochemical state in several diseases. In this study, a rapid, accurate and sensitive method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the targeted analysis of the metabolism of Trp and Tyr has been developed and validated. The method allows for the adequate quantification of Trp, Tyr and, eight Trp metabolites, three Tyr metabolites, together with four competitive large neutral amino acids. Serotonin, 5-hydroxyindoleacetic acid, kynurenine, kynurenic acid, dopamine, and homovanilic acid were among the targeted compounds. Sample preparation, chromatographic separation and mass spectrometric detection were optimized in human urine, human plasma and mice prefrontal cortex extracts. The method was shown to be linear (r > 0.98) in the range of endogenous concentrations for all studied metabolites. In general, the limits of detection were suitable for the detection of the endogenous levels. Intra- and inter-assay precisions below 25% and accuracies ranging from 80 to 120% were found for most of the analytes. The use of labeled internal standards corrected the moderate matrix effect observed for some compounds. The applicability of the method was confirmed by analyzing urine samples collected from 13 healthy volunteers and comparing the results with previously established normal ranges. In addition, urine samples from two patients and a heterozygous carrier of a family with disturbed monoamine metabolism due to a loss of function mutation in the MAOA gene (X-linked) were analyzed and compared with samples from controls. All data together show the potential of the developed approach for targeted metabolomic studies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography A - Volume 1434, 19 February 2016, Pages 91–101
نویسندگان
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