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The Brazilian National Metrology Institute produced a suite of certified reference materials (CRMs) intended as internal standards (ISs) for quantitative nuclear magnetic resonance (qNMR). Being a ratio primary method, the use of qNMR in organic chemistry has already crossed the borders of research laboratories, despite the cost of instrumentation. The International Bureau of Weights and Measures (BIPM) proposed eight potential qNMR ISs. Four candidate materials were selected for their solubility in various solvents and distinct chemical shifts, making them suitable for qNMR analysis of diverse analytes. The certification process compared orthogonal primary methods such as mass balance, qNMR, freezing-point depression, and coulometry, to ensure independent value assignment. Different approaches were compared to assess batch homogeneity and stability. While directly comparing the main compound's chromatographic area proved to be a quick and fit-for-purpose approach, the determination of individual impurities provided lower uncertainties but required more laborious work. CRM batches of maleic acid, dimethyl sulfone, potassium hydrogen phthalate, and dimethyl terephthalate were delivered with over 999.8 mg g -1 purity and uncertainty in the range of 0.6 to 3 mg g -1 (k = 2). The literature shows certification procedures for qNMR ISs whose traceability chain is exclusively based on qNMR measurements. As opposed to that, the methodology presented here provides robust certified values assigned by methods independent of qNMR, in accordance with BIPM recommendations and less prone to qNMR biases. The CRMs developed in this work have already been used for SI-traceable purity evaluation of compounds such as drugs and pesticides, by laboratories in Brazil and abroad., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Certified reference materials (CRM) of amphetamine derivatives were produced through a simple, rapid and efficient synthesis in both batch and continuous-flow conditions, accompanied by the development of a comprehensive certification protocol for this class of substances. Our chemistry enabled the synthesis of MDA, MDMA, PMA and PMMA in two steps from safrole and estragole with overall yields of 38-61 % in 48 hours under batch conditions and 61-65 % in 65 minutes under continuous-flow conditions, followed by the development of a certification protocol for these materials through identity checking, homogeneity, stability, and characterization studies. Furthermore, as result of this work, a very pure CRM of MDA.HCl with 99.1±1.4 g/100 g of certified characterization value was produced. Considering the importance of supplying amphetamine calibrants for public security efforts in Forensic Chemistry, the potential therapeutical applications, and responding to the rising demand for the synthesis of CRM, this work presents a pioneering approach for the production of amphetamine and related compounds., (© 2023 Wiley-VCH GmbH.)

Comparability of measurement results and their metrological traceability to the International System of Units (SI) are fundamental tools to ensure reliable decisions in the social sphere, commerce, and science. The use of appropriate references in analytical chemistry, such as certified reference materials (CRMs) of high purity substances, is one of the required procedures to obtain traceable measurements. When commercial standards with non-certified purity values are used, traceability must be achieved by determining the purity of the standard using a potential primary reference measurement procedure or other appropriate methods. Quantitative nuclear magnetic resonance (qNMR) is a technique with the potential to be used in primary measurement procedures. This work presents the determination of purity by 1 H qNMR for nitrofuran metabolites 3-amino-2-oxazolidinone (AOZ), 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), and 1-aminohydantoin (AHD). Furthermore, a recent qNMR method developed by our group to improve the quantitative performance of measurements using 13 C nucleus was used to determine the purity of semicarbazide (SEM) nitrofuran metabolite. Purity values obtained by qNMR for AOZ, AMOZ, and AHD standards were compared to values obtained by the mass balance approach using a suite of analytical methods: Karl Fischer (KF) coulometric titration and thermogravimetry (TG) for the determination of water and residual solvents, gas and liquid chromatography for the determination of impurities structurally related to the metabolites. The results obtained by qNMR and mass balance were consistent.Graphical abstract.

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.

The design, synthesis and anti HIV-1 replication inhibition of 3-(cyclopropylethynyl)-3-hydroxy-indolin-2-ones, analogues of efavirenz (Sustivatrade mark), are described. Different substituted isatins were used to generate final products that contain pharmacophoric features for RT inhibition, such as the oxoindole and cyclopropylethynyl groups. The suitability of the indolin-2-one ring in the planned compounds in replacement to the benzoxazinone ring of efavirenz was proven, since compound 15 presented a greater activity than efavirenz against HIV-1 replication and was not significantly cytotoxic.

Two galactomannans, one extracted from seeds of Mimosa scabrella, having a mannose to galactose ratio of 1.1, and another with a 1.4 ratio from seeds of Leucaena leucocephala, were sulfated. The products from M. scabrella (BRS) and L. leucocephala (LLS) had a degree of sulfation of 0.62 and 0.50, and an average molecular weight of 620x10(3) and 574x10(3) gmol(-1), respectively. Their activities against yellow fever virus (YFV; BeH111 strain) and dengue 1 virus (DEN-1; Hawaii strain) were evaluated. This was carried out in young mice following intraperitoneal infection with YFV. At a dose of 49 mgkg(-1), BRS and LLS gave protection against death in 87.7 and 96.5% of the mice, respectively. When challenged with 37.5 LD50 of YFV, mice previously inoculated with BRS+virus or LLS+virus, showed 93.3 and 100% resistance, respectively, with neutralization titers similar to mice injected with 25 LD50 of formaldehyde-inactivated YFV. In vitro experiments with YFV and DEN-1 in C6/36 cell culture assays in 24-well microplates showed that concentrations that produced a 100-fold decrease in virus titer of YFV were 586 and 385 mgl(-1) for BRS and LLS, respectively. For DEN-1 they were 347 and 37 mgl(-1), respectively. Sulfated galactomannans, thus demonstrate in vitro and in vivo activity against flaviviruses.