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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2023 · IF 3.4

Stability of diazepam’s phase II metabolites in dried blood spots on filter paper

Lele Wang,Xuezhi Wang,Wenyue Li,Jiajia Liu,Xiukun Yao,Zhiwen Wei,Keming Yun

Phase II metabolites play an important role in diazepam-related cases. The study aimed to assess the stability of diazepam’s phase II metabolites in dried blood spots on filter paper. Methods A piece of filter paper was spotted with 100 µL of whole blood (added 1% sodium fluoride as needed) obtained from participant who received 5 mg diazepam orally, air dried for 2 h at room temperature , and then stored at different conditions. Whole spots were cut at 0.1 cm from the outer edge of blood spots at post-consumption time-points of prior (zero), 5, 16, 35, 61, 120 days and 1, 1.5 years. Analytes were extracted with methanol/water mixture (8:2, v/v) and determined using HPLC-MS/MS. Decomposition rules were analyzed by a statistical software “SPSS”. Results Temazepam glucuronide remained stable (0.5–18.6% loss) at 20 ℃ and at 20 ℃ with 1% sodium fluoride for 16 days, while it was unstable after 5 days at 4 ℃ (21.1–26.2% loss) and − 20 ℃ (28.9 - 34.4% loss). After 35 days, temazepam glucuronide concentrations began to fluctuate significantly under all conditions, and an obvious increase (290.4–355.1%) was observed in 1.5 years. Oxazepam glucuronide was always unstable after 5 days, the percentage loss was even 100% when it was stored for 61 days and 1.5 years. Conclusions Dried blood spots on ordinary filter paper are recommended to be stored at 20 ℃ or 20 ℃ with 1% sodium fluoride within 16 days. Samples should be analyzed immediately or stored in sterile and dry media.

CAS / MDL: 64-18-6
研究领域: 药理学 · 法医学
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Gels · 2025 ·Vol. 11 ·期 6 ·412 · IF 5.3

Effect of Potassium-Ion-Triggered Double Helix Aggregation on Shakedown Behavior of κ-Carrageenan/Polyacrylamide Hydrogel

Xueqi Zhao,Yudong Pan,Zhanrong Zhou,Yang Gao,Aijun Li,Binkai Shi,Jian Hu,Liuying Wang

This study investigates the effect of potassium ion (K+) concentration on double helix aggregation inκ-carrageenan-based hydrogels, which significantly influences their shakedown behavior. The shakedown behavior ofκ-carrageenan/polyacrylamide (PAAm) hydrogels was characterized by the evolution of maximum stress and energy dissipation during cyclic load. The experimental results indicate that higher K+concentrations significantly improve the maximum stress in the steady state, but barely influence the energy dissipation in the steady state. The improved maximum stress can be explained by the higher density of double helix aggregation. The steady energy dissipation elucidates that the K+concentration does not affect the breaking–recovering balance of the sacrificial network in cyclic loading. These results provide mechanistic insights into how ion-triggered double helix aggregation influences the shakedown behavior ofκ-carrageenan-based hydrogels.

研究领域: 材料科学 · 高分子化学 · 生物物理学
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SCIENCE OF THE TOTAL ENVIRONMENT · 2023 · IF 9.8

Flunitrazepam induces neurotoxicity in zebrafish through microbiota-gut-brain axis

Wenting Lin,Kan Li,Yingjun Qin,Xing Han,Xiaohui Chen,Yuan Ren

The abuse of psychoactive substances has led to their frequent detection in the environment, with unknown effects on the nervous system. In this study, zebrafish were exposed to benzodiazepine drug flunitrazepam (FLZ, 0.2 and 5 μg/L) for 30 days to assess its neurotoxicity. Results revealed that FLZ disrupted the balance of gut microbiota and caused an increase in pathogenic bacteria, such as Paracoccus and Aeromonas , leading to pathological damage to the intestine. The upregulation of intestinal pro-inflammatory factors, IL-1β and TNF-α , by 2.4 and 6.3 times, respectively, along with the downregulation of tight junction proteins, Occludin and zonula occludens 1 ( ZO-1 ), by 80 % and 50 %, increased in intestinal permeability. Moreover, untargeted metabolomics demonstrated that FLZ interfered with intestinal nucleotide metabolism and amino acid biosynthesis. FLZ could also increase the levels of lipopolysaccharide (LPS) and malondialdehyde (MDA) in the brain by 0.9 and 3.4 times, respectively, leading to pathological changes in brain tissue. Furthermore, FLZ significantly disturbed nucleotide metabolism and amino acid biosynthesis and metabolism pathways in the brain. Correlation analysis between gut microbiota and neurochemicals confirmed that FLZ can induce neurotoxicity through the microbiota-gut-brain axis. These findings elucidate the molecular mechanisms of psychoactive drugs on microbiota-gut-brain axis and provide a theoretical basis for the ecological environmental risk assessment of various psychoactive substances.

研究领域: 毒理学 · 神经科学 · 环境科学
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TRIBOLOGY LETTERS · 2019 ·Vol. 67 ·期 2 ·58 · IF 2.235

Synthesis of a Multi-phenol Antioxidant and Its Compatibility with Alkyl Diphenylamine and ZDDP in Ester Oil

Jin Yongliang,Duan Haitao,Cheng Bingxue,Wei Lei,Tu Jiesong,Liu Jianfang,Li Jian

In this study, a multi-phenol antioxidant 2,4,6-tris(3,5-di-tert-butyl-4-hydroxyphenylthio)-1,3,5-triazine (THA) was synthesized. The thermal stability of THA and its oxidation resistance in triisodecyl trimellitate (TDTM) ester oil were evaluated compared with several commercial phenol antioxidants. Further investigations on the oxidation resistance and tribological performance of THA with dinonyl diphenylamine (Am) and ZDDP composites were conducted to determine the additive compatibility in TDTM. The results indicate that the THA possesses higher thermal stability and more effectiveness of oxidation resistance than the commercial phenol antioxidants. The synergistic anti-oxidative effect is confirmed for the THA/Am mixtures in TDTM ester oil. However, the addition of THA alone or THA/Am mixtures shows no improvement for the tribological performance of TDTM. Excitingly, the THA/Am/ZDDP composite additives not only have the superior oxidation resistance, but exhibit the effective friction and wear reductions. It suggests the excellent compatibility of the synthesized THA antioxidant with Am and ZDDP additives in TDTM ester oil.

研究领域: 材料化学 · 润滑材料 · 应用化学 · 高分子化学 · 表面科学 · 机械工程 · 石油化学 · 摩擦学
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FUEL · 2023 · IF 7.4

Strategical design of bridged vanillic Schiff-bases as jet fuel antioxidants

Ji Mi,Cui Ye,Yongsheng Guo,Wenjun Fang

Two vanillic Schiff-base antioxidants, 2-methoxy-4-(((4-(phenylamino)phenyl)imino)methyl)phenol (PPIMP) and 2-methoxy-4-(((4-(phenylamino)phenyl)amino)methyl)phenol (PPAMP), have been synthesized through the Schiff-base condensation reaction and hydrogenation to improve the thermal-oxidative stability of hydrocarbon fuels. Both novel antioxidants exhibited remarkable performance in decalin and JP-10 fuel. For example, pressurized differential scanning calorimetry (P-DSC) tests showed that adding 100 ppm of PPIMP or PPAMP to JP-10 improved the oxidation induction time from 9.5 min to 19.2 and 27.8 min, respectively. JFTOT tests showed that adding 100 ppm of either antioxidant helped alleviate JP-10 deposition. Theoretical calculations on electron properties and orbital conformation revealed that the C = N bridge in PPIMP had an electron donation effect and conjugative stabilization effect, which can stabilize intermediate antioxidant radicals and improve the antioxidants’ reactivity. The hydrogenation of C = N further enhanced the performance of PPAMP by introducing an additional antioxidant group. Therefore, both C = N and C-N in the synthesized antioxidants were found to be essential. The chemical combination of small molecular antioxidants achieves 1 + 1 > 2 synergism with the assistance of the azomethine group.

研究领域: 化学 · 材料科学 · 航空航天工程 · 燃料化学
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