BackgroundQuality assurance (QA) and quality control (QC) are two quality management processes that are integral to the success of metabolomics including their application for the acquisition of high quality data in any high-throughput analytical chemistry laboratory. QA defines all the planned and systematic activities implemented before samples are collected, to provide confidence that a subsequent analytical process will fulfil predetermined requirements for quality. QC can be defined as the operational techniques and activities used to measure and report these quality requirements after data acquisition.Aim of reviewThis tutorial review will guide the reader through the use of system suitability and QC samples, why these samples should be applied and how the quality of data can be reported.Key scientific concepts of reviewSystem suitability samples are applied to assess the operation and lack of contamination of the analytical platform prior to sample analysis. Isotopically-labelled internal standards are applied to assess system stability for each sample analysed. Pooled QC samples are applied to condition the analytical platform, perform intra-study reproducibility measurements (QC) and to correct mathematically for systematic errors. Standard reference materials and long-term reference QC samples are applied for inter-study and inter-laboratory assessment of data.

Fetal life evolves in a hypoxic environment. Changes in the oxygen content in utero caused by conditions such as pre-eclampsia or type I diabetes or by oxygen supplementation to the mother lead to increased free radical production and correlate with perinatal outcomes.In the fetal-to-neonatal transition asphyxia is characterized by intermittent periods of hypoxia ischemia that may evolve to hypoxic ischemic encephalopathy associated with neurocognitive, motor, and neurosensorial impairment. Free radicals generated upon reoxygenation may notably increase brain damage. Hence, clinical trials have shown that the use of 100% oxygen given with positive pressure in the airways of the newborn infant during resuscitation causes more oxidative stress than using air, and increases mortality.Preterm infants are endowed with an immature lung and antioxidant system. Clinical stabilization of preterm infants after birth frequently requires positive pressure ventilation with a gas admixture that contains oxygen to achieve a normal heart rate and arterial oxygen saturation. In randomized controlled trials the use high oxygen concentrations (90% to 100%) has caused more oxidative stress and clinical complications that the use of lower oxygen concentrations (30–60%). A correlation between the amount of oxygen received during resuscitation and the level of biomarkers of oxidative stress and clinical outcomes was established. Thus, based on clinical outcomes and analytical results of oxidative stress biomarkers relevant changes were introduced in the resuscitation policies. However, it should be underscored that analysis of oxidative stress biomarkers in biofluids has only been used in experimental and clinical research but not in clinical routine. The complexity of the technical procedures, lack of automation, and cost of these determinations have hindered the routine use of biomarkers in the clinical setting. Overcoming these technical and economical difficulties constitutes a challenge for the immediate future since accurate evaluation of oxidative stress would contribute to improve the quality of care of our neonatal patients.

Instrumental developments in sensitivity and selectivity boost the application of liquid chromatography-mass spectrometry (LC-MS) in metabolomics. Gradual changes in the LC-MS instrumental response (i.e. intra-batch effect) are often unavoidable and they reduce the repeatability and reproducibility of the analysis, decrease the power to detect biological responses and hinder the interpretation of the information provided. Because of that, there is interest in the development of chemometric techniques for the post-acquisition correction of batch effects. In this work, the use of quality control (QC) samples and support vector regression (QC-SVRC) and a radial basis function kernel is proposed to correct intra-batch effects. The repeated analysis of a single sample is used for the assessment of both the correction accuracy and the effect of the distribution of QC samples throughout the batch. The QC-SVRC method is evaluated and compared with a recently developed method based on QC samples and robust cubic smoothing splines (QC-RSC). The results show that QC-SVRC slightly outperformed QC-RSC and allows a straightforward fitting of the SVRC parameters to the instrument performance by using the ε-insensitive loss parameter.

Preterm infants have an immature antioxidant system; however, they frequently require supplemental oxygen. Oxygen-free radicals cause both pulmonary and systemic inflammation, and they are associated with increased morbidity and mortality. Consequently, screening of metabolite profiles representing the amount of lipid peroxidation is considered of great relevance for the evaluation of in vivo oxidative stress and derived inflammation and damage. Ranges for total relative contents of isoprostanes (IsoPs), isofurans (IsoFs), neuroprostanes (NeuroPs), and neurofurans (NeuroFs) within targeted SpO2 ranges were determined in urine samples of 254 preterm infants<32 weeks of gestation within the frame of two randomized, controlled, and blinded clinical trials employing ultra-performance liquid chromatography-tandem mass spectrometry. A total of 536 serial urine samples collected during the first 4 weeks after birth in recruited infants who did not develop free radical associated conditions were analyzed. A reference range for lipid peroxidation byproducts, including isoprostanes, isofurans, neuroprostanes, and neurofurans, was calculated and possible correlations with neonatal conditions were investigated. Urinary elimination of isofurans in the first 4 days after birth correlated with later development of bronchopulmonary dysplasia. Our observations lead to the hypothesis that early urinary determination of lipid peroxidation byproducts, especially isofurans, is relevant to predict development of chronic lung conditions.

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