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The aim of the study was to analyze the process of roasting coffee beans in a convection–conduction roaster (CC) without a heat exchanger and a convection–conduction–radiation roaster (CCR) with a heat exchanger for determination of the aroma profile. The aroma profile was analyzed using the SPME/GC-MS technique, and an Agrinose electronic nose was used to determine the aroma profile intensity. Arabica coffee beans from five regions of the world, namely, Peru, Costa Rica, Ethiopia, Guatemala, and Brazil, were the research material. The chemometric analyses revealed the dominance of azines, alcohols, aldehydes, hydrazides, and acids in the coffee aroma profile. Their share distinguished the aroma profiles depending on the country of origin of the coffee beans. The high content of pyridine from the azine group was characteristic for the coffee roasting process in the convection–conduction roaster without a heat exchanger, which was shown by the PCA analysis. The increased content of pyridine resulted from the appearance of coal tar, especially in the CC roaster. Pyridine has an unpleasant and bitter plant-like odor, and its excess is detrimental to the human organism. The dominant and elevated content of pyridine is a defect of the coffee roasting process in the CC roaster compared to the process carried out in the CCR machine. The results obtained with the Agrinose showed that the CC roasting method had a significant effect on the sensor responses. The effect of coal tar on the coffee beans resulted in an undesirable aroma profile characterized by increased amounts of aromatic volatile compounds and higher responses of Agrinose sensors.

There is a high degree of uncertainty regarding optimum care of patients with potential or known intake of oral anticoagulants and traumatic brain injury (TBI). Anticoagulation therapy aggravates the risk of intracerebral hemorrhage but, on the other hand, patients take anticoagulants because of an underlying prothrombotic risk, and this could be increased following trauma. Treatment decisions must be taken with due consideration of both these risks. An interdisciplinary group of Austrian experts was convened to develop recommendations for best clinical practice. The aim was to provide pragmatic, clear, and easy-to-follow clinical guidance for coagulation management in adult patients with TBI and potential or known intake of platelet inhibitors, vitamin K antagonists, or non-vitamin K antagonist oral anticoagulants. Diagnosis, coagulation testing, and reversal of anticoagulation were considered as key steps upon presentation. Post-trauma management (prophylaxis for thromboembolism and resumption of long-term anticoagulation therapy) was also explored. The lack of robust evidence on which to base treatment recommendations highlights the need for randomized controlled trials in this setting.

A novel method was developed and validated for the quantification of the three approved CDK4/6 inhibitors (abemaciclib, palbociclib, and ribociclib) in both human and mouse plasma and mouse tissue homogenates (liver, kidney, spleen, brain, and small intestine) using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). For all matrices, pretreatment was performed using 50 μL of sample by protein precipitation with acetonitrile, followed by dilution of the supernatant. Chromatographic separation of the analytes was done on a C18 column using gradient elution. A full validation was performed for human plasma, while a partial validation was executed for mouse plasma and mouse tissue homogenates. The method was linear in the calibration range from 2 to 200 ng/mL, with a correlation coefficient (r) ≥0.996 for each analyte. For both human and mouse plasma, the accuracy and precision were within ±15% and ≤15%, respectively, for all concentrations, except for the lower limit of quantification, where they were within ±20% and ≤20%, respectively. A fit-for-purpose strategy was followed for tissue homogenates, and the accuracy and precision were within ±20% and ≤20%, respectively, for all concentrations. Stability of all analytes in all matrices at different processing and storage conditions was tested; ribociclib and palbociclib were unstable in most tissue homogenates and conditions were modified to increase the stability. The method was successfully applied for the analysis of mouse samples from preclinical studies. A new ribociclib metabolite was detected in mouse plasma samples with the same m/z transition as the parent drug.

We have developed a novel, sustainable, and quality-by-design (QbD) driven RP-HPLC method to simultaneously identify pyridine in powder for injection and its degradation products. The goal of this method is to meet the growing demand for robust, eco-friendly methods of quality control for pharmaceutical products. QbD ensured method robustness, while minimizing solvent consumption and waste generation to ensure sustainability. Several sustainable tools were investigated to assess their ecological impact in the study. Using Box-Behnken design, three chromatographic parameters were optimized: column oven temperature, flow rate, and buffer pH. An ethanol and buffer solution mobile phase at pH 6.5 in gradient mode was found to be optimal. An Avantor Hichrom C18 (0.46 cm × 15 cm, 5 µm) column was used with UV detection at 254 nm and pumped at 1.0 mL/min. The linearity of pyridine occurred in the 0.13–40 µg/mL range with an R 2 of 0.9999. Pyridine was tested for acidity, basicity, oxidation, sunlight, and heat according to rules are set forth by the International Council for Harmonization (ICH). Degradation caused by bases, acids, and oxidation provided the highest degradation rates. Incorporating quality-by-design principles with sustainability considerations makes this method robust, eco-friendly, and cost-effective for quality control in pharmaceutical products. Having been successfully applied to powder of injection, its utility in the pharmaceutical industry is unquestionable.

The four cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, ivacaftor, lumacaftor, tezacaftor, and elexacaftor, have revolutionised the treatment of CF by direct action on the protein target behind the disease’s development. The aim was to develop and validate a quantification method for these CFTR modulators in plasma and breast milk to better understand inter-patient variability in pharmacokinetics and treatment outcome, including the risk of adverse drug reactions. The ability to monitor CFTR modulators in breast milk enables the estimation of the exposure of breastfed infant, with a potential concern for CFTR modulator-induced liver injury. The analysis was performed on a Thermo Vanquish Flex Binary UHPLC system coupled to a high-resolution mass spectrometer (HRMS), Thermo Q Exactive. The analytes were detected using positive electrospray ionisation in full scan mode. After sample preparation by protein precipitation, the supernatant was injected onto the LC system and the analytes were separated using a Zorbax SB-C18 Rapid Res HPLC column (3.5 µm, 4.6 × 75 mm). This is the first published method for CFTR modulators in breast milk. The validated quantification range for ivacaftor is 0.0050–10 µg/mL with a coefficient of variation < 6% and a mean accuracy of 97–106%; for lumacaftor, tezacaftor, and elexacaftor, the validated quantification range is 0.050–100 µg/mL with a coefficient of variation < 8% and a mean accuracy 93–106%. A simple and sensitive quantification method for CFTR modulators has been developed and used for routine analysis of human plasma and breast milk samples since 2022.

The photodegradations of three selected neonicotinoid insecticides nitenpyram, thiacloprid, and acetamiprid were investigated in both water and soil samples under natural sunlight, UVA light, and UVB light. The results indicate that these insecticides undergo significant degradations when subjected to sunlight, whether they are in deionized (DI) water, tap water, and DI water containing 100 mg/L humic acids or in soil. The degradation half-lives of nitenpyram, thiacloprid, and acetamiprid in tap water under sunlight were found to be 3.7, 4.7, and 8.9 h, respectively, in DI water 5.4, 6.3, 9.1 h, respectively, in DI water containing 100 mg/L humic acids 3.6, 3.3, 6.5 h, respectively, and in soil 7.5, 7.9, and 15.9 h, respectively. The degradation due to hydrolysis was found insignificant as compared to photodegradation. The examination of the effects of light source revealed that the UVB in the sunlight plays a major role in the photodegradation of these three neonicotinoids, and the effects of UVA and visible light are negligible. The analysis on the degradation products indicated that the nitroguanidine group in these insecticides is unstable and prone to break up under sunlight. A total of nine degradation products were detected, of which the health effects and the fate and transport in the environment need to be further studied.

According to EU guidance SANCO/7525/VI/95 Rev. 10.3, residue data extrapolation from a surrogate major crop to a minor crop can be used for setting maximum residue levels (MRLs) with a reduced number of residue trials and representative selected pesticides. In this work, a QuEChERS method (citrate-buffered version and PSA with MgSO4 clean-up) and LC-ESI-MS/MS for the determination of boscalid, pyraclostrobin, fludioxonil, fluopyram and tebuconazole in persimmon was developed and validated according to EU Commission guidelines and afterwards used for the determination of residues in four field trials. Residue levels at harvest for each pesticide ranged between 0.347 and 0.028 mg/kg. After comparing EFSA residue data on apples, as the surrogate major crop, and conducting a consumer risk assessment, a proposal of residue data extrapolation to set MRLs in persimmons was performed. The results showed that pesticide residues in persimmons at harvest were consistently lower than residues in apples when substances were applied according to the same critical GAP. MRLs were set at 0.5 mg/kg for fludioxonil, 0.6 mg/kg for boscalid, 0.3 mg/kg for tebuconazole, 0.4 mg/kg for fluopyran and 0.3 mg/kg for pyraclostrobin. The ratio of the MRLs for apple/persimmon varied between 2.5 for boscalid and 1.25 for fluopyram, suggesting that residue extrapolation can be feasible, promoting the process of pesticide registration for minor crops and the settlement of MRL.

Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity.

Organic luminescent solids are attracting increasing interest in various fields of application 1 , 2 , 3 . Modification or alteration of the chemical structures of their component molecules is the most common approach for tuning their luminescence properties. However, for dynamic tuning or switching of solid-state luminescence with high efficiency and reproducibility successful examples are limited 2 , 4 as chemical reactions in the solid state frequently encounter insufficient conversion, one-way reactions or loss of their luminescence properties. One promising approach is to control the luminescence properties by altering the mode of solid-state molecular packing without chemical reactions. Here, we show that 2,2′:6′,2′′-terpyridine 5 , practically non-luminescent in the form of amorphous solid or needle crystal 6 , shows strong blue luminescence upon formation of a plate crystal. Efficient and reproducible on–off switching of solid-state luminescence is demonstrated by heat-mode interconversion between the plate and needle crystals. Because alteration of the mode of molecular packing does not require chemical reactions, the present findings would open the way for the development of novel organic luminescent solids that can be switched on and off by external thermal stimuli.

Purpose This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration. Methods Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair. Results Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1 month after intake, were 0.033–0.037 pg/hair strand (0.17–0.19 pg/mg) for SUV and 0.054–0.28 pg/hair strand (0.28–1.5 pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study. Conclusions This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.