Laboratory interpretative comments and guidance: clinical and operative outcomes on moderate to severe hyponatraemia patient management.

AIMS: Hyponatraemia is the most common body fluid disorders but often goes unnoticed. Our laboratory incorporated a standardised procedure to help clinicians detect moderate/severe hyponatraemia. The study aims were to evaluate the outcomes on patient care and clinicians' satisfaction. METHODS: The study, observational and retrospective, included 1839 cases, adult and paediatric patients, with sodium concentration <130 mmol/L. The procedure consisted of interpretative comments in the emergency and core laboratories report and the point-of-care testing blood gas network report. We evaluated hyponatraemia length in two equal periods: before and after the implementation. We conducted a survey addressed to the staff of the clinical settings involved to know their satisfaction. RESULTS: The median hyponatraemia length decreased significantly from 4.95 hours (2.08-16.57) in the first period to 2.17 hours (1.06-5.39) in the second period. The lack of hyponatraemia patients follow-up was significantly less after the procedure implementation. The survey was answered by 92 (60 senior specialists and 32 residents) out of 110 clinicians surveyed. Ninety of them (98%) answered positively. CONCLUSIONS: We have demonstrated the reduction in the time for diagnosing and management by physicians, the higher uniformity in the time required to solve hyponatraemia episodes following our laboratory procedure and the clinicians' satisfaction.

Determination of up to twenty carboxylic acid containing compounds in clinically relevant matrices by o-benzylhydroxylamine derivatization and liquid chromatography-tandem mass spectrometry.

Carboxylic acid containing compounds (R-COOH) are involved in a large number of biological processes and they are relevant for several pathological processes such as neurodegeneration or cancer. Comprehensive methodologies for the quantitative determination of R-COOH in biological samples are required. In this study we have developed a LC-MS/MS method for the quantification of 20 endogenous R-COOH belonging to different pathways such as kynurenine metabolism, serotoninergic pathway, glycolysis, tricarboxylic acid cycle, dopaminergic pathway, short chain fatty acids and glycine metabolism. The approach included derivatization with o-benzylhydroxylamine (reaction time 1 h), liquid-liquid extraction with ethyl acetate and LC-MS/MS detection (run time 10 min). The method was optimized and validated in 5 different matrices (urine, plasma, saliva, brain and liver) following two different approaches: (i) using surrogate matrices and (ii) using actual human samples by standard additions. A suitable linearity was obtained in the endogenous range of the analytes. Adequate intra and inter-assay accuracies (80-120%) and intra- and inter-assay precisions (<20%) were achieved for almost all analytes in all studied matrices. The method was applied in several scenarios to confirm (i) human urinary changes produced in glycolysis after exercise, (ii) metabolic changes produced in rat brain and plasma by methamphetamine administration and (iii) metabolic alterations in human plasma caused by vitamin B6 deficiency. Additionally, the application of the method allowed for establishing previously unreported alterations in R-COOH metabolites under these conditions. Due to the comprehensive analyte and matrix coverage and the wide applicability of the developed methodology, it can be considered as a suitable tool for the study of R-COOH status in health and disease by targeted metabolomics.

Nail Melatonin Content: A Suitable Non-Invasive Marker of Melatonin Production.

Melatonin plays multiple physiological roles in the human body. Evaluation of melatonin production by the determination of urinary 6-sulfatoxymelatonin in 24-h samples has important drawbacks which hinder the successful evaluation of melatonin production in large cohorts. Here, we evaluated the potential of nail analysis for estimating melatonin production. Firstly, mass spectrometry methodology for the determination of melatonin in nails was optimized and successfully validated. The method was found to be linear in the range 6.5-830 fg/mg with intraday and interday accuracy in the range 100-104 %, precision below 15 % and a LOD of 3.5 fg/mg. Secondly, nail melatonin concentrations from 84 volunteers (age 5-96) were determined. The expected correlation between melatonin and age was obtained (correlation coefficient -0.615; p < 0.001). Additionally, we showed that fingernails are preferable to toenails to determine nail melatonin content. Finally, fingernails collected for 180 days after melatonin administration (two volunteers, 1.9 mg/night during 5 days) were analyzed. Nail melatonin concentrations immediately rose after administration and went back to pre-administration values after ≈100 days in both volunteers. Our results suggest that melatonin determination in nails is a suitable non-invasive tool for the estimation of global melatonin production. Due to the easy collection and storage of nails, the long-term information obtained and the multiple functions of melatonin, nail melatonin content might complement dim light melatonin onset, which is commonly measured from plasma/saliva samples, paving the way for melatonin research.