JOURNAL OF CHEMICAL AND ENGINEERING DATA
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2024
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IF 2
Jingxuan Qiu,Jing Lin,Chaoqun Zhang,Liping Zhao,Peng Wang,Jia Zhang,Rui Zhang,Yunchun Guo,Huiliang Wang
In this paper, the solubility of furosemide in 12 monosolvents including methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, 1-pentanol, acetone, 2-butanone, methyl acetate, ethyl acetate, and water was measured by using a static gravimetric method within the temperature range of 283.15 to 323.15 K under atmospheric pressure. The solubility magnitudes show an increasing tendency with the increase of temperature in all solvents. Within the entire temperature range, the solubility is the lowest in water (0.0053 × 10–3 at 283.15 K) and the highest in 1-pentanol (72.736 × 10–3 at 323.15 K). The rough subsequence of solubility is 1-pentanol > methanol > n-propanol > ethanol > isopropanol > sec-butanol > n-butanol in alcoholic solvents and acetone >2-butanone > methyl acetate > ethyl acetate > water in nonalcohol solvents. The solubility behavior of furosemide is a result of the combined effects of solvent polarity, solvent–solvent intermolecular interactions (characterized by cohesive energy density), and summation of hydrogen bond acceptor propensities. Moreover, the experimental solubility data were fitted by the models of Apelblat and Yaws. The results indicate that the two models could both correlate the experimental values satisfactorily, and the Yaws model is more appropriate to fit the solubility data of furosemide compared with the Apelblat model.
研究领域:
药学
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物理化学
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DOI
高影响因子
CRYSTAL GROWTH & DESIGN
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2021
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IF 4.076
Maolin Li,Mengwei Wang,Yumin Liu,Ruiling Ouyang,Mingdi Liu,Dandan Han,Junbo Gong
Furosemide (FUR) is usually used to treat congestive heart failure and edema. Although bioavailability problems exist due to its poor solubility and unstable gastrointestinal absorption, preparing FUR/amino acid (AA) co-amorphous systems is regarded as a promising way to solve this problem. In this work, the oscillating ball milling method was successfully used to prepare the co-amorphous systems of FUR with l-cysteine, l-phenylalanine (PHE), l-arginine, l-tryptophan (TRP), and l-valine. Protonation of the secondary amino group (N2) in FUR probably results in interactions with the AA carboxyl group, which lead to excellent compatibility between FUR and AAs. The co-amorphous systems formed between FUR and PHE/TRP possess higher physical stability than other FUR/AA co-amorphous systems, which may be attributed to favorable aromatic stacking in FUR/PHE and FUR/TRP systems. Additional experiments were performed to explore the impact of co-former loadings on the stability of co-amorphous systems, which revealed that the co-amorphous systems are most stable when the molar ratios are at 0.527 and 0.423 for FUR in FUR/PHE and FUR/TRP systems, respectively. Finally, powder dissolution tests of the FUR/PHE and FUR/TRP co-amorphous systems were carried out, and the results demonstrated that the selected most stable co-amorphous systems have excellent dissolution advantage with a two-fold improvement of dissolution rate compared to pure FUR.
研究领域:
药剂学
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药物化学
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DOI
高影响因子
MOLECULES
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2023
·Vol. 28
·期 5
·2415
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IF 4.6
Ao Xu,Yunlin Xue,Yuyu Zeng,Jing Li,Huiling Zhou,Zhen Wang,Yin Chen,Hui Chen,Jian Jin,Tao Zhuang
Furosemide is a widely used loop diuretic in the treatment of congestive heart failure and edema. During the preparation of furosemide, a new process-related impurity G in the levels ranging from 0.08% to 0.13% was detected in pilot batches by a new high performance liquid chromatography (HPLC) method. The new impurity was isolated and characterized by comprehensive analysis of FT-IR, Q-TOF/LC-MS, 1D-NMR (1H,13C, and DEPT), and 2D-NMR (1H-1H-COSY, HSQC, and HMBC) spectroscopy data. The possible formation pathway of impurity G was also discussed in detail. Moreover, a novel HPLC method was developed and validated for the determination of impurity G and the other six known impurities registered in the European Pharmacopoeia as per ICH guidelines. The HPLC method was validated with respect to system suitability, linearity, the limit of quantitation, the limit of detection, precision, accuracy, and robustness. The characterization of impurity G and the validation of its quantitative HPLC method were reported for the first time in this paper. Finally, the toxicological properties of impurity G were predicted by the in silico webserver ProTox-II.Keywords:furosemide;process-related impurity;characterization;Q-TOF/LC–MS and NMR;method validation
研究领域:
药物化学
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分析化学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Saige Meng,Shuangqing Wang,Ming Guan Piao
The synergistic gastroretentive drug delivery systems are capable of delivering drugs with a narrow absorption window. The purpose of this study is to prepare furosemide hollow-bioadhesive microspheres to improve bioavailability. The emulsion solvent volatilization method was adopted, through Box-Behnken design, with polymer ratio (X 1 ), dosage (X 2 ), organic solvent volume (X 3 ) and PVA concentration (X 4 ) as independent variables, and drug loading (Y 1 ), encapsulation rate (Y 2 ), yield rate (Y 3 ) and 8 h floating rate (Y 4 ) were response variables. The interaction effects of the independent and response variables were explored. The optimized hollow-bioadhesive microspheres showed the in vitro floating rate of 93.33 ± 5.24% for 8 h, the in vitro retention rate of 90.67 ± 3.21%, and the sustained drug release of 93.79 ± 4.90% for 12 h. Compared with the hollow microspheres, the hollow-bioadhesive microspheres significantly increase the retention time in the stomach. The results of Differential Scanning Calorimetry , Fourier Transform InfraRed, and X-ray diffraction showed that furosemide had good biocompatibility with excipients. Compared with commercial tablets, the relative bioavailability of hollow-bioadhesive microspheres was increased by 163.84%, and the long-term therapeutic concentration was maintained. The safety evaluation proved the oral safety of microspheres. In conclusion, the safe and economical furosemide hollow-bioadhesive microsphere is a valuable preparation for development, which can improve clinical application.
研究领域:
药剂学
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药物递送系统
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生物医学工程
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DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
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2024
·Vol. 47
·期 14
·2400003
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IF 2.8
Kunlin He,Qian Chen,Xueling Chen,Chungu Zhang,Shun Feng,Lianhai Shan
Furosemide (FUR), banned in sports events by the World Anti-Doping Agency, is a key target in drug tests, necessitating a pretreatment material capable of selectively, rapidly, and sufficiently separating/enriching analytes from complex matrices. Herein, a metal-mediated magnetic molecularly imprinted polymer (mMIP) was rationally designed and synthesized for the specific capture of FUR. The preparations involved the utilization of chromium (III) as the binding pivot, (3-aminopropyl)triethoxysilane as functional monomer, and Fe 3 O 4 as core, all assembled via free radical polymerization. Both the morphologies and adsorptive properties of the mMIP were characterized using multiple methods. The resulting Cr(III)-mediated mMIP (ChM-mMIP) presented excellent selectivity and specificity toward FUR. Under optimized conditions, the adsorption capacity reached 128.50 mg/g within 10 min, and the imprinting factor was 10.41. Moreover, it was also successfully applied as a dispersive solid-phase extraction material, enabling the detection of FUR concentration as low as 20 ng/mL in human urine samples when coupled with a high-performance liquid chromatography/photodiode array. Overall, this study offers a valuable strategy for the development of novel recognition material.
研究领域:
分析化学
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材料科学
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药学
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体育科学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
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2022
·Vol. 14
·期 11
·2307
·
IF 6.525
Xueyan Gou,Fenglin Ran,Jinru Yang,Yanrong Ma,Xin’an Wu
Background: Organic anion transporter 1 (OAT1) and OAT3 have an overlapping spectrum of substrates such that one can exert a compensatory effect when the other is dysfunctional. As a result, the knockout of either OAT1 or OAT3 is not reflected in a change in the excretion of organic anionic substrates. To date, only the mOAT1 and mOAT3 individual knockout mouse models have been available. Methods: In this study, we successfully generated aSlc22a6/Slc22a8double-knockout (KO) rat model using CRISPR/Cas9 technology and evaluated its biological properties. Results: The double-knockout rat model did not expressionmRNAfor rOAT1 or rOAT3 in the kidneys. Consistently, the renal excretion ofp-aminohippuric acid (PAH), the classical substrate of OAT1/OAT3, was substantially decreased in theSlc22a6/Slc22a8double-knockout rats. The relativemRNAlevel ofSlco4c1was up-regulated in KO rats. No renal pathological phenotype was evident. The renal elimination of the organic anionic drug furosemide was nearly abolished in theSlc22a6/Slc22a8knockout rats, but elimination of the organic cationic drug metformin was hardly affected. Conclusions: These results demonstrate that this rat model is a useful tool for investigating the functions of OAT1/OAT3 in metabolic diseases, drug metabolism and pharmacokinetics, and OATs-mediated drug interactions.Keywords:OAT1/OAT3;CRISPR/Cas9;gene knockout;pharmacokinetic
研究领域:
药理学
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分子生物学
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遗传学
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药物发现
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2025
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IF 4.7
Yue-Ming Yu,Lu Liu,Fan-Zhi Bu,Zhi-Long Zhao,Zhi-Yong Wu,Yan-Tuan Li
The combination of cardiotonic milrinone (MLN) and diuretics furosemide (FSM) is used to treat refractory heart failure clinically. However, the compatibility and stability issues of both limit the curative effect. For highlighting the superiority of cocrystallization technology in regulating drug performances, further getting new understanding for developing dual-drug cocrystals to realize their combination at the molecular level, a cocrystallization-driven drug-drug bidirectional optimization tactic is presented. By cocrystallizing MLN and FSM into the same lattice, for one thing, the in vitro/vivo properties of MLN can be optimized, and the photostability of FSM is raised simultaneously, thereby enhancing the bioavailability, and creating a prerequisite for the bidirectional optimization and the combination of these two drugs at the molecular level. Based on this, the dual-drug cocrystal MLN-FSM is successfully assembled and thoroughly characterized by multiple techniques. The evaluations of in vitro/vivo properties involving theory and experiment methods exhibit that the garnered cocrystal has achieved the simultaneous improvements in solubility and permeability versus pure MLN; meanwhile, the cocrystal formation also prominently enhances the stability of FSM relative to FSM itself. Interestingly, these bidirectional optimized in vitro properties change into in vivo pharmacokinetic strengths effectively, showcasing the raised bioavailability and extended half-life, thus laying a solid foundation for exerting the combined effect of the two drugs at the molecular level. Therefore, this research provides the first dual-drug cocrystal solid form with clinical combination drugs to treat cardiac failures, also offers innovative insights into leveraging the advantages of the cocrystallization-driven strategy for fulfilling the co-treatment of clinical combination drugs from the molecular levels.
研究领域:
药学
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晶体工程
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药物传递
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药物化学
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药理学
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DOI
高影响因子
PeerJ
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2017
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IF 2.177
Hang Lu,Zhiqiang Lu,Xue Li,Gentao Li,Yilin Qiao,Robert P. Borris,Youcai Zhang
Background Herb-drug interactions (HDIs) resulting from concomitant use of herbal products with clinical drugs may cause adverse reactions. Organic anion transporter 1 (OAT1) and 3 (OAT3) are highly expressed in the kidney and play a key role in the renal elimination of substrate drugs. So far, little is known about the herbal extracts that could modulate OAT1 and OAT3 activities. Methods HEK293 cells stably expressing human OAT1 (HEK-OAT1) and OAT3 (HEK-OAT3) were established and characterized. One hundred seventy-two extracts from 37 medicinal and economic plants were prepared. An initial concentration of 5 µg/ml for each extract was used to evaluate their effects on 6-carboxylfluorescein (6-CF) uptake in HEK-OAT1 and HEK-OAT3 cells. Concentration-dependent inhibition studies were conducted for those extracts with more than 50% inhibition to OAT1 and OAT3. The extract of Juncus effusus , a well-known traditional Chinese medicine, was assessed for its effect on the in vivo pharmacokinetic parameters of furosemide, a diuretic drug which is a known substrate of both OAT1 and OAT3. Results More than 30% of the plant extracts at the concentration of 5 µg/ml showed strong inhibitory effect on the 6-CF uptake mediated by OAT1 (61 extracts) and OAT3 (55 extracts). Among them, three extracts for OAT1 and fourteen extracts for OAT3 were identified as strong inhibitors with IC 50 values being <5 µg/ml. Juncus effusus showed a strong inhibition to OAT3 in vitro , and markedly altered the in vivo pharmacokinetic parameters of furosemide in rats. Conclusion The present study identified the potential interactions of medicinal and economic plants with human OAT1 and OAT3, which is helpful to predict and to avoid potential OAT1- and OAT3-mediated HDIs.
研究领域:
药理学
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毒理学
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植物科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2022
·
IF 8.943
Nan Zhang,Yan Gao,Kangjia Sheng,Xianliang Xu,Wanghui Jing,Tao Bao,Sicen Wang
Herein, corncob waste was used as a scaffold for the fabrication of effective adsorbents. Porphyrinic zirconium metal-organic frameworks (MOFs) PCN-223 and PCN-224 constructed by different numbers of Zr6 cluster nodes were grown on the surface of the corncob. Fe (Ш) ions were implanted in the porphyrin ring by post-synthesis modification. The results showed that the extraction capacity of diuretics on [email protected] containing suitable pore size was larger than that of [email protected] The adsorption of diuretics was further enhanced because of the electrostatic effect caused by implantation of Fe (Ш) ions. [email protected] was recyclable and selective for the extraction of furosemide (Fur) and bumetanide (Bum). Coupled in-syringe solid phase extraction (IS-SPE) with ultra-performance liquid chromatography (UPLC), an efficient, sensitive, and stable method was established. With a sensitivity between 0.6 and 1.0 μg/L and a recovery between 83.2% and 119.2%, it is used for the analysis of trace amounts of Fur and Bum in weight loss products and environmental water. The functionalized corncob has potential application for the adsorption of diuretics, and the metal ions implantation in MOFs provides a promising strategy for enhancing extraction capacity.
研究领域:
材料科学
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环境化学
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分析化学
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废物管理
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2019
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IF 4.561
Shanghong Zong,Bochen Pan,Leping Dang,Hongyuan Wei
In this work, pure form I and form II of furosemide-4,4′-bipyridine (FS-4BPY) 2:1 cocrystals were prepared. Both polymorphs were characterized by optical microscopy , powder X-ray diffraction, differential scanning calorimetry , thermogravimetric analysis , and Fourier transform infrared spectroscopy . The relative stability of the two forms was estimated from their solubility data in 2-propanol by the gravimetric method. Moreover, the thermodynamically stable form with lower solubility, form II, was further investigated in different pure and binary solvents from 293.15 K to 333.15 K under atmospheric pressure. In pure solvent system, the solubilities of forms II cocrystals increase with rising temperature and follow the order of acetone > ethanol > 1-propanol ≈ 1-butanol > 2-propanol > acetonitrile . In 2-propanol–water binary solvent system, the co-solvency phenomenon was observed and the maximum solubility of form II is higher than that in pure solvents. The experimental solubility data were correlated by the modified Apelblat model, the CNIBS/R–K model, the Jouyban–Acree model and the NRTL model, and all models give satisfactory correlations. Finally, the apparent dissolution thermodynamic properties, including the dissolution Gibbs energy , the dissolution enthalpy and the dissolution entropy, were calculated based on the NRTL model. The results indicate that the dissolution processes of form I and form II of FS-4BPY cocrystals in selected solvents are all spontaneous, endothermic, and entropy-driven.
研究领域:
药学
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物理化学
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热力学
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晶体学
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产品关联
DOI
高影响因子
Journal of Cleaner Production
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2026
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IF 10.7
Rui Hu,Hao-Tong Zheng,Boxi Tang,Jialing Tu,Yu-Hong Cui,Xuedong Zhai,Gang Wen,Zheng-Qian Liu
Effluent organic matter (EfOM) from municipal wastewater treatment plants is an emerging concern because of its refractory and potential risk to ecological environment. Herein, this investigation comprehensively evaluated the effects of HO • and O 3 exposures on EfOM transformation and micropollutant degradation under different pre-coagulation operating conditions during ozonation. Compared to coagulation and ozonation alone, coupling two processes could effectively reduce total organic carbon, color and UV 254 of effluent. Fe-based coagulant was easier to combine with OH − to generate floc in bulk than Al-based coagulant for EfOM capture, which could decrease total scavenging capacities of effluents as well as increase the exposures of O 3 and HO • during ozonation, enhancing ozonation efficiency for EfOM degradation. EfOM from membrane bioreactor treatment was more difficult to capture during pre-coagulation but more easily degraded during ozonation than that from conventional activated sludge treatment due to its lower molecular weight distribution and higher contents of humic-like and tryptophan-like substances. Parallel factor analysis shows that coagulation combined with ozonation breaks the fluorescent groups of humic-like and tryptophan-like substances effectively. Molecular weight distribution determination indicates that coupling two processes could more effectively remove humic-like substances, organic colloids and polysaccharides compared to coagulation or ozonation alone. Furthermore, micropollutants with higher energy of highest occupied molecular orbital were degraded more efficiently during ozonation. The investigation reveals that O 3 utilization efficiency for micropollutant degradation can be significantly improved by pre-coagulation, offering new ideas for reducing energy consumption during advanced ozonation treatment and ensuring the safety of effluent and sustainable water reuse.
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产品关联
DOI
高影响因子
Autophagy
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2022
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IF 13.391
Yuhua Zhang,Qiaojun Fang,Hongfeng Wang,Jieyu Qi,Shan Sun,Menghui Liao,Yunhao Wu,Yangnan Hu,Pei Jiang,Cheng Cheng,Xiaoyun Qian,Mingliang Tang,Wei Cao,Shang Xiang,Chen Zhang,Jianming Yang,Xia Gao,Zheng Ying,Renjie Chai
Aminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. In the current study, we found that PINK1-PRKN-mediated mitophagy was impaired in neomycin-treated hair cells. Our data suggested that mitochondrial recruitment of PRKN and phagophore recognition of damaged mitochondria during mitophagy were blocked following neomycin treatment. In addition, the degradation of damaged mitochondria by lysosomes was significantly decreased as indicated by the mitophagic flux reporter mt-mKeima. Moreover, we demonstrated that neomycin disrupted mitophagy through transcriptional inhibition of Pink1 expression, the key initiator of mitophagy. Moreover, we found that neomycin impaired mitophagy by inducing ATF3 expression. Importantly, treatment with a mitophagy activator could rescue neomycin-treated hair cells by increasing mitophagy, indicating that genetic modulation or drug intervention in mitophagy may have therapeutic potential for aminoglycoside-induced hearing loss.Abbreviations: AAV: adeno-associated virus; ABR: auditory brainstem response; ATF3: activating transcription factor 3; ATOH1/MATH1: atonal bHLH transcription factor 1; BafA1: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; COX4I1/COXIV: cytochrome c oxidase subunit 4I1; CTBP2/RIBEYE: C-terminal binding protein 2; DFP: deferiprone; EGFP: enhanced green fluorescent protein; FOXO3: forkhead box O3; GRIA2/GLUR2: glutamate receptor, ionotropic, AMPA2 (alpha 2); HC: hair cell; HSPD1/HSP60: heat shock protein 1 (chaperonin); IHC: inner hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MYO7A: myosin VIIA; OPTN: optineurin; OMM: outer mitochondrial membrane; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; RT-qPCR: real-time quantitative polymerase chain reaction; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling; USP30: ubiquitin specific peptidase 30; XBP1: X-box binding protein 1.
研究领域:
细胞生物学
·
神经科学
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耳科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）