Abstract
Simultaneous determination of kynurenines, neurotransmitters, pterins and steroids linked to various neurological and metabolic diseases have important diagnostic significance for related pathology and drug monitoring. An improved, sensitive and selective ultra-high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometric (UHPLC-MS/MS) method, based on our earlier publication, has been proposed for the quantitative measurement of 42 metabolites in human urine. The assay covers a larger number of analytes, uses an advanced, Waters Atlantis T3 chromatographic column and similarly meets the guideline of European Medicines Agency (EMA) on bioanalytical method validation. Analytical performance met all the EMA requirements and the assay covered the relevant clinical concentrations. Linear correlation coefficients were all > 0.998. Intra-day and inter-day accuracy and precision were 87−118%, 81−120% and 2–20%, respectively including the lower limit of quantification (LLOQ). The assay is expected to facilitate the diagnosis and allows drug level monitoring from urine.
Highlights
Neurotransmitters, kynurenines and pterins play important role for various neurologic, metabolic and psychiatric disorders [1,2,3]
The metabolic pathway starting from the amino acids phenylalanine and tyrosine (TYR) results in synthesis of several neurotransmitters that play a fundamental role in maintaining brain physiological function
A quantitative determination of some diagnostically important molecules in human serum and CSF has already been presented in our previous study [11] based on the guideline of European Medicines Agency (EMA) on bioanalytical method validation [12]. Using this methodology we aimed to develop an extended method for measuring urine samples using of an improved chromatographic separation and wider range of analytes
Summary
Neurotransmitters, kynurenines and pterins play important role for various neurologic, metabolic and psychiatric disorders [1,2,3]. Concur rent measurement of these metabolites in human serum, cerebrospinal fluid (CSF) and urine helps to diagnose diverse diseases and gives op portunity to better understand differences in metabolic pathways. 95% of the tryptophan metabolism results in the formation of kynurenines. Differences in this metabolic pathway may play an important role in the course of diverse neurological diseases [9]. The metabolic pathway starting from the amino acids phenylalanine and tyrosine (TYR) results in synthesis of several neurotransmitters that play a fundamental role in maintaining brain physiological function
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