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The present work describes a multi-residue SPE-UPLC–MS/MS method aiming at the characterization of 68 compounds in natural waters, including parent compounds as well as their major metabolites and glucuronide conjugates. Development was conducted toward the quantitative determination of a broad range of analytes belonging to different class of psychotropic drugs such as benzodiazepines, antidepressants, stimulants, opiates and opioids, anticonvulsants, anti-dementia drugs, analgesic and anti-inflammatory drugs (as anthropic indicators) in the low ng L −1 range of concentration. Satisfactory extraction recoveries >70% were obtained for the majority of analytes (49 out of 68) allowing low limits of quantification. LOQ ranged between 0.1 and 17.8 ng L −1 and were lower than 5 ng L −1 for 94% of investigated analytes. Furthermore, addition of 25 isotopic labeled standards allowed to ensure reliability of the optimized method. Quantification errors were typically below 15% with relative standard variations <10% in intermediate precision conditions. Finally, the developed method was implemented in natural waters; sampling campaigns were conducted in the Seine River as a demonstration of the applicability and adequation of the method for its purpose. As a result, 48 out of 68 analytes were identified or quantified; some of them like memantine, rivastigmine, zolpidem 4-phenyl-carboxylic acid, zolpidem 6-carboxylic acid for one of the first time in surface waters. Among investigated psychotropic compounds and metabolites, tramadol, codeine, oxazepam, venlafaxine, O -desmethylvenlafaxine, gabapentin, carbamazepine and 10,11-dihydro-10,11-dihydroxycarbamazepine were found to be the most abundant. [ABSTRACT FROM AUTHOR]

Objectives: In clinical pratice, tau protein measurement generally relies on immunoassays (IAs), whose major drawback is the lack of results comparability due to differences in selectivity and/or calibration. This underlines the importance of establishing a traceability chain for total tau (t-tau) measurements. The objective of this work is to develop a higher order candidate reference measurement procedure (RMP) for the absolute quantification of t-tau in cerebrospinal fluid (CSF)., Methods: To calibrate the candidate RMP and establish metrological traceability to the SI units, a primary calibrator consisting in a highly purified recombinant protein was sourced. Its purity was evaluated by liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) and the protein mass fraction in solution was certified by amino acid analysis (AAA). An isotopically-labelled homologue was obtained to develop a candidate RMP by isotope dilution mass spectrometry (IDMS) for t-tau absolute quantification in CSF. Calibration blends and quality control (QC) materials were gravimetrically prepared and subjected to the same preparation workflow as CSF samples, followed by LC-HRMS analysis in Parallel Reaction Monitoring (PRM) mode., Results: A primary calibrator has been developed and an IDMS candidate RMP has been validated for CSF t-tau. The candidate RMP was used to certify t-tau concentration in three pools of CSF (low, medium, high)., Conclusions: The candidate RMP will pave the road towards global standardization of CSF t-tau measurements. Together with commutable Certified Reference Materials (CRMs), it will allow evaluating and improving the accuracy and comparability of results provided by IAs., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

The quantification of low abundant proteins in complex matrices by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) remains challenging. A measurement procedure based on optimized antibody-free sample preparation and isotope dilution coupled to LC-MS/MS was developed to quantify procalcitonin (PCT) in human serum at sub-microgram per liter level. A combination of sodium deoxycholate-assisted protein precipitation with acetonitrile, solid-phase extraction, and trypsin digestion assisted with Tween-20 enhanced the method sensitivity. Linearity was established through peptide-based calibration curves in the serum matrix (0.092-5.222 μg/L of PCT) with a good linear fit (R2 ≥ 0.999). Quality control materials spiked with known amounts of protein-based standards were used to evaluate the method's accuracy. The bias ranged from -2.6 to +4.3%, and the intra-day and inter-day coefficients of variations (CVs) were below 2.2% for peptide-based quality controls. A well-characterized correction factor was determined and applied to compensate for digestion incompleteness and material loss before the internal standards spike. Results with metrological traceability to the SI units were established using standard peptide of well-characterized purity determined by peptide impurity corrected amino acid analysis. The validated method enables accurate quantification of PCT in human serum at a limit of quantification down to 0.245 μg/L (bias -1.9%, precision 9.1%). The method was successfully applied to serum samples obtained from patients with sepsis. Interestingly, the PCT concentration reported implementing the isotope dilution LC-MS/MS method was twofold lower than the concentration provided by an immunoassay., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Over two decades, the Organic Analysis Working Group (OAWG) of the Consultative Committee for Amount of Substance: Metrology in Chemistry and Biology (CCQM) has organized a number of comparisons for clinically relevant small molecule organic biomarkers. The aim of the OAWG community is to be part of the coordinated international movement towards accuracy and comparability of clinical measurements that will, in turn, minimize the wastage of repeat testing and unnecessary therapy to create a sustainable healthcare industry. International and regional directives/requirements on metrological traceability of calibrators and control materials are in place. Metrology institutes worldwide maintain infrastructure for the practical realization of metrological traceability and demonstrate the equivalence of their measurement capabilities through participation in key comparisons organized under the auspices of the CCQM. These institutes provide certified reference materials, as well as other dedicated value-assignment services benefiting the in-vitro diagnostic (IVD) industry, reference (calibration) laboratories and the clinical chemistry laboratories. The roles of these services in supporting national, regional, and international activities to ensure the metrological traceability of clinical chemistry measurements are described. Graphical abstract.

Pesticides are used worldwide with potential harmful effects on both fauna and flora. The Kibale National Park in Uganda, a site renowned for its biodiversity is surrounded by tea, banana and eucalyptus plantations as well as maize fields and small farms. We previously showed presence of pesticides with potential endocrine disruptive effects in the vicinity. To further investigate the water pollution linked to agricultural pressure in this protected area, we implemented a complementary monitoring strategy based on: analytical chemistry, effects based methods and the deployment of Polar Organic Chemical Integrative Samplers (POCIS). Chemical analysis of the POCIS extracts revealed the presence of 13 pesticides: carbofuran, DEET, 2.4-D amine, carbaryl, ametryn, isoproturon, metolachlor, terbutryn, dimethoate, imidacloprid, picaridin, thiamethoxam, carbendazim, with the first three being present in the largest quantities. Water samples collected at the POCIS sampling sites exhibited thyroid and estrogen axis disrupting activities in vivo, in addition to developmental and behaviour effects on Xenopus laevis tadpoles model. Based on our observations, for the health of local human and wildlife populations, further monitoring as well as actions to reduce agrochemical use should be considered in the Kibale National Park and in regions exposed to similar conditions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Research on emerging substances in drinking water presents major interest and the possibility of trace contamination has seen increasing concern from the scientific community and the public authorities. More particularly, residues of pharmaceuticals and personal care products (PPCPs) in bottled water are a very important issue due to societal concerns and potential media impact. In this context, it has become necessary to carry out reliable monitoring. This requires measurements of high quality with demonstration of accuracy and well-defined uncertainty. In this study, 20 pharmaceutical compounds were targeted for the first time in 167 bottled waters from France and other European countries. An isotope dilution-solid phase extraction-liquid chromatography mass spectrometry method, together with stringent quality control and quality assurance protocols, was developed and validated according to French mandatory standards. Recoveries between 87% and 112% were obtained with coefficient of variation below 20%. Operational limits of quantification (LOQ) were comprised between 5 and 30ngL -1 . Expanded uncertainties (k=2) ranged between 16% and 43% and were below 35% for half of the compounds. The survey showed only four positive quantifications, thereby highlighting the rarity of contamination., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most common form of dementia in humans, and a major public health concern with 35 million of patients worldwide. Cerebrospinal fluid (CSF) biomarkers being early diagnostic indicators of AD, it is essential to use the most efficient analytical methods to detect and quantify them accurately. These biomarkers, and more specifically amyloid-β (Aβ) peptides, are measured in routine clinical practice using immunoassays. However, there are several limits to this immunodetection in terms of specificity and multiplexing of the multiple isoforms of the Aβ peptides. To overcome these issues, the quantification of these analytes by mass spectrometry (MS) represents an interesting alternative, and several assays have been described over the past years. This article reviews the different Aβ peptides quantitative MS-based approaches published so far, compares their pre-analytical phase, and the different quantitative strategies implemented that might be suitable for clinical applications.

Objectives: Our objective was to develop a reference method to measure total cholesterol in human serum, in order to assign values and assess the accuracy of field methods in French clinical laboratories., Design and Methods: A reference method based on gas chromatography coupled with mass spectrometry and isotope dilution (GC-IDMS) was developed and validated. It was then used to assign reference values to five frozen serum samples from voluntary proficiency testing schemes gathering 170 French clinical laboratories. Three peer groups were defined and bias against the reference method target value was calculated., Results: Accuracy of the reference method was assessed against NIST SRM 1951b. Bias of the reference method was less than 0.5% and imprecision was less than 1.0%. Our study indicated that field methods tended to overestimate total cholesterol concentration, mean bias being +5.02% ± 1.02%. The most popular methods (phenolic chromogen with spectrophotometric detection, 80% of participants) exhibited the highest bias (peer group mean bias: +5.51 ± 1.24%). Neither these methods nor those using a non-phenolic chromogen with reflectometric detection (10% of participants, peer group mean bias: +4.20 ± 1.44%) met NCEP recommendations according to which bias should be less than 3%. Only the methods using a non phenolic chromogen with a spectrophotometric detection met these recommendations (10% of participants, peer group mean bias: +1.39 ± 2.75%)., Conclusions: As all three peer groups provided positively biased results, the consensus mean usually used to assess the trueness of routine methods is biased as well, which results in an erroneous estimation of method bias. Therefore, this study highlights the value added by reference method target values to assess trueness of field methods and monitor performance of clinical laboratories., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The reliability of biological tests is a major issue for patient care in terms of public health that involves high economic stakes. Reference methods, as well as regular external quality assessment schemes (EQAS), are needed to monitor the analytical performance of field methods. However, control material commutability is a major concern to assess method accuracy. To overcome material non-commutability, we investigated the possibility of using lyophilized serum samples together with a limited number of frozen serum samples to assign matrix-corrected target values, taking the example of glucose assays. Trueness of the current glucose assays was first measured against a primary reference method by using human frozen sera. Methods using hexokinase and glucose oxidase with spectroreflectometric detection proved very accurate, with bias ranging between -2.2% and +2.3%. Bias of methods using glucose oxidase with spectrophotometric detection was +4.5%. Matrix-related bias of the lyophilized materials was then determined and ranged from +2.5% to -14.4%. Matrix-corrected target values were assigned and used to assess trueness of 22 sub-peer groups. We demonstrated that matrix-corrected target values can be a valuable tool to assess field method accuracy in large scale surveys where commutable materials are not available in sufficient amount with acceptable costs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Matrix Reference Materials (MRM) are essential tools for the validation of analytical protocols. Nowadays, there are no such materials for the determination of herbicides in water. So, a feasibility study of a MRM for the analysis of triazines and phenylureas in water was carried out. Different kinds of candidates MRM were prepared: solutions of pesticides diluted in acetonitrile and stored in sealed vials or stored at the dry state after the evaporation of the solvent to dryness, pesticides stored on two different types of polymeric solid-phase extraction (SPE) sorbents after the percolation of drinking or river waters spiked with pesticides. The stability of these candidates MRM stored at various temperatures (room temperature, 0.5 degrees C or -18 degrees C) was studied over a period of approximately 1 year. Two different levels of concentration were studied for each kind of material. During the storage, some samples of each different MRM candidate were monthly analyzed by liquid chromatography. Results showed that, among the candidate materials, some of them presented satisfactory enough stability to consider a further certification. They were either pesticides in solution in sealed vials or pesticides stored on cartridges after the percolation of spiked water samples. However, it was shown that these different MRM candidates had to be stored at a temperature lower than 0.5 degrees C.