Linagliptin is a highly specific, long‐acting inhibitor that is used as an orally administrable agent for type‐2 diabetes treatment. Because only the R‐enantiomer is of clinical use, we developed a ...capillary electrophoresis method for the determination of the enantiomeric impurity of this compound. Carboxymethyl‐β‐cyclodextrin was selected as the chiral selector for the separation of linagliptin enantiomers. Design of experiments and desirability functions were used for the analytical optimization, which was focused on understanding and improving the electrophoretic process. The effects of significant parameters (background electrolyte concentration and pH, cyclodextrin concentration, temperature, and voltage) were thoroughly investigated. The complete separation of linagliptin and its enantiomeric impurity with baseline resolution was achieved within 10 min on an uncoated fused‐silica capillary (50 μm inner diameter, 365 μm outer diameter, 64.5/56 cm in total/ effective length) maintained at 25°C, under an applied voltage of 28.0 kV. The background electrolyte contained 70 mM sodium acetate and 4.7 mM carboxymethyl‐β‐cyclodextrin, and the pH was adjusted to 6.10. The method was validated, and a limit of quantitation of 0.05% for the impurity was estimated.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Obesity and associated liver disease are a growing public health concern. Pharmacological agents to treat non-alcoholic fatty liver disease are limited. FGF21, a hormone secreted by the liver and ...potent metabolic modulator, is a promising therapeutic target for this indication with several analogs currently in clinical development. However, concerns about a negative effect of FGF21 on female fertility have not been fully addressed.
After induction of obesity, female C57BL/6N mice received a 7-day course of subcutaneously administered FGF21. Control groups received either high-fat diet (HFD) or a normal diet (ND). The mothers were then mated with lean males for 12 weeks. The estrous cycle was recorded for two weeks after breeding. The metabolic phenotype, liver steatosis and reproductive organs were assessed at sacrifice 14 weeks after treatment.
A short-course treatment of FGF21 leads to weight reduction during treatment but has no long-term impact on liver steatosis. A treatment with FGF21 leads to a reduction in the number of pregnancies (0 vs 1, p = 0.019) and no viable pup was born to a mother previously treated with FGF21. The FGF21 treatment affected the number of cycles (1 vs 3, p = 0.048) and amount in diestrus (54 vs 75%, p = 0.008) 12 weeks after the treatment. Additionally, the number of corpora lutea (0.8 vs 3.0, p = 0.016), and mature follicles (0 vs 1, p = 0.037) was reduced compared to the ND group while uterine histology remained unaffected.
A short-term treatment with FGF21 has a long-term effect on female fertility in mice. This represents a potential safety concern for FGF21 analogs currently in clinical development. Reproductive health outcomes should be included in upcoming clinical trials.
FGF21; Fertility; Non-alcoholic fatty liver disease; High-fat diet.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A simple, cost‐effective, and greener HPLC method was investigated to determine 14 β‐lactams. To achieve this, various strategies were implemented such as the use of an aqueous mobile phase, ionic ...liquids, or an alternative organic solvent. Preliminary experiments were conducted using “one‐factor‐at‐a‐time” to identify the significant factors affecting chromatographic performance. The experimental design (central composite design) was then applied to thoroughly examine the effects of the key factors and exploit them to achieve optimal HPLC condition. The developed method was less hazardous and improved the retention and peak shape, compared with other conventional methods. The optimized assay condition was validated according to the ICH guidelines and effectively applied for the quantification of some β‐lactams in various formulations. These results imply that this novel HPLC method can be employed for routine analyses of some β‐lactams in pure drug and commercial formulations.
Combination of Green analytical chemistry and Experimental design in the determination of β‐lactams.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Despite their young age, Generation Z has high awareness and experience of using e-wallets, otherwise known as digital wallets. However, research on users’ behaviours is often conducted in the ...context of the older Millennial generation, which has many different characteristics and behaviours in their use of the new technical e-wallet. This research aims to examine how technical barriers and promoting factors impact Generation Z’s intention to adopt an e-wallet service to hold their money and make frictionless payments. Based on the technology acceptance model (TAM), this study examines 170 Generation Z students who were born between 1995 and 2005. The results show that the relationship between promoting factors and intention to use the e-wallet has been mediated by perceived usefulness, while the barrier factor has a direct influence on intention to use.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The study of the pressure response by NMR spectroscopy provides information on the thermodynamics of conformational equilibria in proteins and nucleic acids. For obtaining a database for expected ...pressure effects on free nucleotides and nucleotides bound in macromolecular complexes, the pressure response of 1H chemical shifts and J-coupling constants of the purine 5′-ribonucleotides AMP, ADP, ATP, GMP, GDP, and GTP were studied in the absence and presence of Mg2+-ions. Experiments are supported by quantum-chemical calculations of populations and chemical shift differences in order to corroborate structural interpretations and to estimate missing data for AMP. The preference of the ribose S puckering obtained from the analysis of the experimental J-couplings is also confirmed by the calculations. In addition, the pressure response of the non-hydrolysable GTP analogues GppNHp, GppCH2p, and GTPγS was examined within a pressure range up to 200 MPa. As observed earlier for 31P NMR chemical shifts of these nucleotides the pressure dependence of chemical shifts is clearly non-linear in most cases. In di- and tri-phospho nucleosides, the resonances of the two protons bound to the ribose 5′ carbon are non-equivalent and can be observed separately. The gg-rotamer at C4′- C5′ bond is strongly preferred and the downfield shifted resonance can be assigned to the H5″ proton in the nucleotides. In contrast, in adenosine itself the frequencies of the two resonances are interchanged.
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•1H chemical shifts of purine 5′- ribonucleotides at pressures up to 200 MPa.•The pressure response of the 1H chemical shifts is non-linear.•The 5′ protons were stereospecifially assigned; errors in literature were corrected.•The conformational equilibria were studied experimentally.•Quantum-chemical calculation of AMP fit well to the experiments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This research combined ultrasonic-assisted extraction (UAE) and natural deep eutectic solvent (NADES) to recover phenolic and flavonoid components from mangosteen rind. The antioxidant activities ...were determined using DPPH, ABTS+, and hydroxyl assays. NADES prepared from lactic and 1,2–propanediol had the highest extraction efficiency based on the total flavonoid content (TFC) and phenolic contents (TPC). Single-factor experiments were employed to assess the influence of UAE conditions (liquid-to-solid ratio, temperature, water content in NADES, and time) on TFC, TPC, and antioxidant activities. NADES-based UAE conditions were optimized using response surface methodology with the Box-Behnken design model on five dependent responses (TPC, TFC, DPPH, ABTS, and OH). The optimal conditions for the lactic-1,2–Propanediol-based UAE process were 76.7 ml liquid/g solid with 30.3% of water content at 57.5 °C for 9.1 min. Scanning electron microscopy (SEM) was applied to examine the surface morphology of mangosteen rind before and after sonication. This study proposes an efficient, green, and practical approach for recovering phenolics and flavonoids from mangosteen rinds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant ...activity was examined. The extraction yields of NADES-based UAE were assessed based on the yields of phenolics and flavonoids extracted from the black mulberry fruit. This study selected the molar ratios of hydrogen bond acceptors (HBA) and hydrogen bond donors HBD at 1:2 from previous studies. Choline chloride-lactic acid showed the highest solubility with phenolics and flavonoids among NADES systems. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio (LSR), water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. The suitable NADES-based UAE conditions for extracting phenolics and flavonoids from the black mulberry fruit were 60 ml/g of LSR, 40% water content, 70 °C, and 15 min. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9 °C, and 24.2 min of extraction time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy (SEM) was used to survey the surface of black mulberry fruit with and without sonication. SEM can assist in demonstrating the destructive effect of NADES and ultrasonic waves on material surfaces. SEM findings indicated the high surface destruction capacity of NADES, which partially contributed to a superior extraction yield of NADES than conventional organic solvents. The study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits. The black mulberry fruit extracts can be applied to meat preservation and beverages with high antioxidants.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A simple, specific, and economical LC-MS/MS method was investigated for the screening of 43 prescribed antihypertensive and related drugs in human urine. The urine samples were simply prepared by ...diluting and mixing with internal standard before directly introduced to the LC-MS/MS system, which is fast, straightforward, and cost-effective. Fractional factorial, Box-Behnken, and I-optimal design were applied to screen and optimize the mass spectrometric and chromatographic factors. The analysis was carried out on a triple quadrupole mass spectrometer system utilizing multiple reaction monitoring with positive and negative electrospray ionization method. Chromatographic separation was performed on a Thermo Scientific Accucore RP-MS column (50 × 3.0 mm ID., 2.6 ㎛) using two separate gradient elution programs established with the same mobile phases. Chromatographic separation was performed within 12 min. The optimal method was validated based on FDA guideline. The results indicated that the assay was specific, reproducible, and sensitive with the limit of detection from 0.1 to 50.0 ㎍/L. The method was linear for all analytes with coefficient of determination ranging from 0.9870 to 0.9981. The intra-assay precision was from 1.44 to 19.87% and the inter-assay precision was between 2.69 and 18.54% with the recovery rate ranges from 84.54 to 119.78% for all drugs measured. All analytes in urine samples were stable for 24 h at 25℃, and for 2 weeks at -60℃. The developed method improves on currently existing methods by including larger number of cardiovascular medications and better sensitivity of 12 analytes.
A simple, specific, and economical LC–MS/MS method was investigated for the screening of 43 prescribed antihy-pertensive and related drugs in human urine. The urine samples were simply prepared by ...diluting and mixing with internal stan-dard before directly introduced to the LC-MS/MS system, which is fast, straightforward, and cost-effective. Fractional factorial, Box-Behnken, and I-optimal design were applied to screen and optimize the mass spectrometric and chromatographic factors. The analysis was carried out on a triple quadrupole mass spectrometer system utilizing multiple reaction monitoring with posi-tive and negative electrospray ionization method. Chromatographic separation was performed on a Thermo Scientific Accucore RP-MS column (50 × 3.0 mm ID., 2.6 µm) using two separate gradient elution programs established with the same mobile phases. Chromatographic separation was performed within 12 min. The optimal method was validated based on FDA guideline. The results indicated that the assay was specific, reproducible, and sensitive with the limit of detection from 0.1 to 50.0 µg/L.
The method was linear for all analytes with coefficient of determination ranging from 0.9870 to 0.9981. The intra-assay preci-sion was from 1.44 to 19.87% and the inter-assay precision was between 2.69 and 18.54% with the recovery rate ranges from 84.54 to 119.78% for all drugs measured. All analytes in urine samples were stable for 24 h at 25 o C, and for 2 weeks at -60 o C. The developed method improves on currently existing methods by including larger number of cardiovascular medications and better sensitivity of 12 analytes. KCI Citation Count: 0
Abstract
Preservatives are often utilized to prevent growth of bacteria and extend shell-life of personal care products (PCPs). This causes an increase in the number of cases of allergic contact ...dermatitis to preservatives. This study focused on the determination of two isothiazolinones (MI and MCI) in PCPs by HPLC-DAD. Different pretreatment methods were examined for different sample matrices. Recoveries were over 80% with %RSD < 6% in three studied sample matrices (wet tissue, shampoo and cream) at three different spiked levels. The method was applied to determine MI and MCI in 84 PCPs (shampoo, shower gel, cream,
etc
.) purchased in Ho Chi Minh City, Vietnam from March to July in 2021. MI and MCI were detected in some PCPs.
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