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Objective: To describe the role of biochemical anomalies of tyrosine (TYR), tryptophan (TRP), and arginine (ARG) metabolism in patients suffering from episodic and chronic cluster headache (CCH). Background: The pathogenesis of cluster headache (CH) and the process that transforms the episodic into the chronic form are unknown. However, the accompanying symptoms suggest a dysfunction of the sympathetic system and hypothalamus along with anomalies of metabolism of catecholamines, elusive amines, and nitric oxide (NO) metabolism. Methods: We describe the results obtained from the last papers published on this issue. The level of metabolites were analyzed by different high‐performance liquid chromatography methods. Results: In both episodic and CH patients, the levels of dopamine and elusive amines are very elevated. The only biochemical difference found in studies between episodic and chronic cluster was that norepinephrine levels were significantly lower in episodic cluster in comparison to control and chronic subjects. In addition, the levels of ARG, homoarginine, and citrulline, precursors of synthesis of NO, were significantly lower in chronic cluster. Conclusions: All these results suggest that TYR, TRP, and ARG metabolism is abnormal and may constitute a biochemical fingerprint of CH patients. The increased levels of norepinephrine in chronic cluster constitute a possible cause of chronicity of this primary headache. The high levels of tryptamine and its activity on the central serotoninergic system may explain why the length of CH is brief in comparison to migraine and tension‐type headache. The low levels of ARG, homoarginine, and citrulline may be the consequence of high circulating levels of α1‐agonists, such as epinephrine and norepinephrine, and their biochemical interaction with endothelial trace amine‐associated receptor 1 that induces activation of NO synthase, resulting in NO synthesis in the circulation, NO release, intense vasodilation, and as a result, the cluster attack. [ABSTRACT FROM AUTHOR]

Acylcarnitine profiling in dried blood spots (DBS) is a useful method for high-throughput newborn screening of metabolic disorders, but differentiation of isobaric and isomeric compounds is not achievable. Chromatographic methods for separation have already been reported but are specific for short-chain acylcarnitines or time-consuming. The aim of this work was to develop a fast ultraperformance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method for separation and quantification of a large number of acylcarnitines, including dicarboxylic acylcarnitines and hydroxyacylcarnitines, in DBS and plasma samples. Acylcarnitines from DBS and plasma were converted to their butyl esters and analyzed by electrospray ionization MS/MS. Chromatographic separation was achieved using a UPLC system equipped with an ethylene-bridged hybrid C column. The correlation coefficients of the calibration curves ( r) ranged from 0.990 to 0.999. The limit of detection ranged from 0.002 and 0.063 μM for all compounds, and the limit of quantification ranged from 0.004 and 0.357 μM. Precision ranged from 0.8 to 8.8 % and the mean recovery was 103 %. Profiles of acylcarnitine isomers were investigated in specimens obtained from patients diagnosed with different inborn errors of metabolism. Acylcarnitine concentrations were also measured in 58 term newborns and compared with flow injection analysis measurements. With this newly developed UPLC-MS/MS method, the simultaneous detection of 61 (13 of these labeled) acylcarnitines in DBS and plasma can be achieved in 15 min including postrun equilibration. The method has been validated and can be used as an important component of newborn screening methods as a second-tier test for discrimination and to confirm diagnosis. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Background: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) formation inhibitor, has emerged as a promising biomarker of NO-associated endothelial dysfunction in cardiovascular diseases as well in chronic renal failure. The interest in potentially fundamental role of this metabolite, in basic and clinical research, led to the development of numerous analytical methods for the quantitative determination of ADMA and dimethylarginines in biological systems, notably plasma, serum and urine. Objectives: The aim of this work was to present a simple, fast and accurate UPLC–tandem-MS-based method for the simultaneous determination and quantification of arginine, ADMA, SDMA, NMMA, homo-arginine and citrulline. This method is designed for high sample throughput of only 10μL of human plasma, serum or urine. Methods: The analysis time is reduced to 1.9min by an ultrahigh-performance liquid chromatography run coupled with electrospray ionization (ESI) in the positive mode tandem mass spectrometry detection. Results: The method was validated in plasma, serum and urine. Correlation coefficients (r 2) of the calibration curves in all matrices considered ranged from 0.9810 to 0.9993. Inter- and intra-assay precision, accuracy, recovery and carry-over were evaluated for validation. The LOD was 0.01μM for all compounds in water, plasma and serum and 0.1μM in urine. The LOQ was 0.05μM for ADMA, SDMA, NMMA and H-Arg and 0.5μM for Arg and Cit in water, plasma and serum; while in urine was 0.1μM for ADMA, SDMA, NMMA and H-Arg and 0.5μM for Arg and Cit. The precision was ranged from 1% to 15% expressed as CV% and the accuracy (bias %) was <±7% for all added concentrations with the exception of NMMA (−10%). ADMA mean plasma levels, measured in healthy adults and newborns, were in accord with literature data published: (M±SD) 0.56±0.10μM and 0.84±0.21μM, respectively, showing that ADMA levels in plasma decreased with age. In serum we have similar data (0.54±0.18μM and 1.14±0.36μM), while in neonatal urine ADMA was 11.98±7.13μmolmmol−1 creatinine. Conclusions: Data from calibration curves and method validation reveal that the method is accurate and precise. The fast run time, the feasibility of high sample throughput and the small amount of sample required make this method very suitable for routine analysis in the clinical setting. [Copyright &y& Elsevier]