JOURNAL OF MOLECULAR LIQUIDS
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2022
·
IF 6.633
Shuai Yu,Zihao Wang,Yuanchang Ma,Fumin Xue
Natural polymer additives including ethyecellulose (EC), hydroxy propyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), and sodium lignin sulfonate (SLS) were selected to modify the crystal form and morphology of clozapine crystals. The effects of cooling crystallization, anti-solvent crystallization and additives on clozapine crystal morphology were studied. The type of additive has an obvious effect on the morphology of crystal, while the dosage of additive has a great effect on the average particle size of crystal. Medicinal crystal form of clozapine anhydrate can be obtained after enhanced drying of clozapine monohydrate. Clozapine crystal particles with controllable crystal form, morphology and particle size can be prepared by anti-solvent crystallization method with additive. To further explore the mechanism of natural polymer additives on morphology regulation, molecular simulation was used to analyze the interaction between the main crystal surface, solvent and additives.
研究领域:
药学
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材料科学
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DOI
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Xinding Yao,Zhenwei Wang,Yue Geng,Hongkun Zhao,Elaheh Rahimpour,William E. Acree,Abolghasem Jouyban
Solubility and relevant thermodynamic properties as well as molecular interactions of clozapine in aqueous systems of protic cosolvent, e.g. isopropanol, and aprotic cosolvents such as acetonitrile, dimethyl sulfoxide (DMSO) and N -methyl-2-pyrrolidinone (NMP) are focus of this paper. The intermolecular interactions and overall charge distribution of clozapine were respectively investigated by using Hirshfeld surface analysis and molecular electrostatic potential surface. All experimentations were executed using a shake-flask approach under p = 101.2 kPa (local pressure) from 278.15 (293.15) to 323.15 (333.15) K. The minimum solubility data of clozapine appeared in neat water for each aqueous system at 278.15 K; and the maximum one, in neat cosolvent at 328.15 K. Correlation of the solubility data (mole fraction) through Jouyban–Acree and MRS models acquired acceptable results with relative average deviations ( RAD ) of no>9.15 %. The solvent descriptors of hydrogen-bonding basicity, solubility parameter and dipolarity-polarizability predominantly controlled the clozapine solubility variation through the quantitative analysis of linear solvation energy relationships in terms of the solubility data at 298.15 K. The extended Hildebrand solubility approach was also employed here to correlate the solubility and study the solvation behavior of solutions. Quantitatively analysis of preferential solvation of clozapine by solvent species in solutions was conducted by the method of inverse Kirkwood–Buff integrals. In the solutions with middle and cosolvent-rich compositions, the parameters of preferential solvation for DMSO, NMP, acetonitrile or isopropanol were positive, which specified that preferential solvation of clozapine was made by co-solvent. In addition, the thermodynamic properties of dissolution of clozapine along with enthalpy–entropy compensation were derived and deeply discussed.
研究领域:
药学
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物理化学
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产品关联
DOI
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
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2021
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IF 3.178
Yi Gong,Yueru Wang,Zibo Huang,Jiao sha,Yu Li,Tao Li,Baozeng Ren
In this article, laser monitoring technology was used to study the solubility of clozapine in 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, ethanol, n-propanol, n-butanol, n-pentanol, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, n-pentyl acetate under the pressure of 0.1 MPa (at 278.15 K–323.15 K). Obviously, the mole fraction solubility of clozapine is positively correlated with the increase of experimental temperature. KAT-LSER model was used to study the solvent effect of clozapine solubility in 12 pure solvents. The results show that the interaction of solvent–solute is mainly due to the dipolarity/polarizability and solvent’s self-cohesiveness. The interaction between solute–solvent molecules was analysed by MD simulation, and the results show that the interaction between solute–solvent molecules has an important influence on the solubility of clozapine. Then the solubility data of clozapine were put into five classical thermodynamic models for simulation, namely the λh model, Apleblat model, NRTL model, Margules model and UNIQUAC model. The values calculated by the five solubility models are in good agreement with the measured solubility, it means that the five models have a higher level of simulation accuracy. On the other hand, the apparent thermodynamic properties of clozapine dissolved in solvent were calculated by van’t Hoff equation, the results show that the dissolution process of clozapine in solvents is an endothermic and driven by enthalpy.
研究领域:
药理学
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物理化学
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计算化学
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DOI
高影响因子
Results in Chemistry
·
2025
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IF 4.2
Kejun Liu,Zhizhong Xu,Jianfeng Zhang,Kaining Zhang,Chunyan Wen,Jindong Chen,Qingjiang Lin,Xianhua Zhang
Dahuang-Gancao decoction (DGD) comprises Rhei Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma at ratio of 4:1, which is usually applied for relieving clozapine-induced constipation in clinical practice. However, the herb-drug interactions involving antipsychotics with narrow therapeutic range have rarely been reported. We investigated a potential pharmacokinetic-based interaction between DGD and clozapine based on in vitro and in vivo studies. Rats received a single injection of clozapine (5 mg/kg, i.v. ,) 30 min after pretreatment with DGD ( p.o. ) for 3 days or 14 days. The concentrations of clozapine and its metabolites in rat plasma were measured by high-performance liquid chromatography-tandem mass spectrometry. The effects of DGD on protein expression of cytochrome P450 (CYP450) in vivo and the binding of plasma proteins to clozapine in vitro were determined. After 3-day pretreatment with DGD, there were no significant changes in the pharmacokinetics of clozapine or its metabolites. A significant increase in certain pharmacokinetic parameters of clozapine was observed after 14-day pretreatment with DGD. Protein expression of CYP1A2 was inhibited via multiple dosage of DGD in time-dependent manner. The plasma protein binding rate in various concentrations of clozapine was reduced significantly in vitro after DGD therapy. The effects upon pharmacokinetics of clozapine after DGD pretreatment could be attributed to inhibition of CYP1A2 expression and a decrease in plasma protein binding. Hence, caution must be applied to some drugs with a narrow therapeutic index to avoid the potential risk of herb-drug interactions in clinical practice.
研究领域:
药物代谢
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临床药理学
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中药学
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神经精神药理学
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药物相互作用
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产品关联
DOI
高影响因子
DIAMOND AND RELATED MATERIALS
·
2024
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IF 4.3
Chuanqin Zhou,Yingyu Sima,Yiyong Wu,Yanping Wei,Du Tuo,Shuting Shi,Aiting Chen,Nana Tang,Quanguo He,Wu Wang
Clozapine is vital for managing schizophrenia and other psychiatric disorders. As a potent medication with risks of severe side effects, accurate detection ensures effective treatment monitoring, patient safety, and optimization of therapeutic outcomes. Herein, niobium carbide two-dimensional transition metal carbides (Nb 2 CT x MXene) was prepared by etching niobium aluminum carbide (Nb 2 AlC), which was next partially oxidized by a hydrothermal method to niobium oxide (Nb 2 O 5 )/Nb 2 CT x and ultrasonically bound to carboxylated multi-walled carbon nanotubes (MWCNTs-COOH). It was modified onto a glassy carbon electrode for the detection of the antipsychotic drug clozapine ingested by humans. The morphology and electrochemical properties of MXene-based nanocomposite electrode were verified by scanning electron microscopy, X-ray diffractometry, Raman, cyclic voltammetry and electrochemical impedance characterization methods. The results showed that electrode responded well to clozapine solutions, with good linearity ( R 2 = 0.9979 and 0.9995) of the peak currents with clozapine concentrations (0.01–1.0 μM and 1.0–10.0 μM) and that this sensor had good immunity, repeatability, reproducibility and stability. The limit of detection was 8.38 nM and the recovery was 92.5 % ~ 106.5 % in real serum and urine samples. The MXene-based sensors offer excellent analytical performance and hold promise for cost-effective generalisation to the detection of nanomolar clozapine in a variety of clinical applications.
研究领域:
分析化学
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医学检测
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材料科学
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产品关联
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2024
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IF 4.3
Jun Feng,Pei Zhou,Chunli Qin,Ruijue Chen,Qiying Chen,Lina Li,Jun Chen,Hao Cheng,Wenyi Huang,Jinru Cao
Determination of antiepileptic drugs and antipsychotics in human serum is significant in individualized drug administration and therapeutic drug monitoring (TDM). In this study, we developed a rapid label-free TDM method for the antiepileptic drug carbamazepine (CBZ) and the antipsychotic clozapine (CLO) in human serum. This detection strategy is based on the combination of surface-enhanced Raman scattering (SERS) and magnetic solid-phase extraction (MSPE). Initially, Fe 3 O 4 @SiO 2 @MIL-101(Fe) nanocomposites were synthesized by the layer-by-layer self-assembly method and characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Brunauer–Emmett–Teller, ultraviolet–visible, and Fourier transform infrared analyses. Subsequently, CBZ and CLO were detected in human serum using Fe 3 O 4 @SiO 2 @MIL-101(Fe) as the solid-phase extraction adsorbent and Ag nanoparticles as SERS substrates. The potential of the MSPE–SERS method for the label-free TDM of CBZ and CLO was then investigated. Fe 3 O 4 @SiO 2 @MIL-101(Fe) prevents magnetic particle aggregation and demonstrates rapid magnetic separation capability that simplifies the pretreatment process and reduces interference from complex matrices. Its large surface area can effectively enrich targets in complex matrices, thereby improving the SERS detection sensitivity. The linearity between CBZ and CLO was excellent over the concentration range of 0.1–100 µg/mL (calculated as the intensity of the SERS characteristic peaks of CBZ and CLO at 728 cm and 1054 cm −1 , respectively), with correlation coefficients (R 2 ) of 0.9987 and 0.9957, and detection limits of 0.072 and 0.12 µg/mL, respectively. The recoveries of CBZ with CLO ranged from 94.0 % to 105.0 %, and their relative standard deviations were <6.8 %. Compared to other assays, the developed MSPE–SERS method has the advantages of simple sample pretreatment, rapid detection, and good reproducibility, which provides a novel approach for the TDM of other drugs.
研究领域:
分析化学
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药物监测
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 9
·2739
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IF 4.927
Kai Wang,Luoxing Yang,Huili Huang,Ning Lv,Jiyang Liu,Youshi Liu
Rapid and highly sensitive determination of clozapine (CLZ), a psychotropic drug for the treatment of refractory schizophrenia, in patients is of great significance to reduce the risk of disease recurrence. However, direct electroanalysis of CLZ in human whole blood remains a great challenge owing to the remarkable fouling that occurs in a complex matrix. In this work, a miniaturized, integrated, disposable electrochemical sensing platform based on the integration of nanochannel arrays on the surface of screen-printed carbon electrodes (SPCE) is demonstrated. The device achieves high determination sensitivity while also offering the electrode anti-fouling and anti-interference capabilities. To enhance the electrochemical performance of SPCE, simple electrochemical polarization including anodic oxidation and cathodic reduction is applied to pretreat SPCE. The electrochemically polarized SPCE (p-SPCE) exhibits an enhanced electrochemical peak signal toward CLZ compared with bare SPCE. An electrochemically assisted self-assembly method (EASA) is utilized to conveniently electrodeposit a vertically ordered mesoporous silica nanomembrane film (VMSF) on the p-SPCE, which could further enrich CLZ through electrostatic interactions. Owing to the dual signal amplification based on the p-SPCE and VMSF nanochannels, the developed VMSF/SPCE sensor enables determination of CLZ in the range from 50 nM to 20 μM with a low limit of detection (LOD) of 28 nM (S/N = 3). Combined with the excellent anti-fouling and anti-interference abilities of VMSF, direct and sensitive determination of CLZ in human blood is also achieved.
研究领域:
分析化学
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生物医学工程
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药物分析
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Yuying Chen,Qingwei He,Huangjie Lu,Jie Yang,Jiongming Han,Ying Zhu,Ping Hu
This study addresses the challenging task of quantitatively investigating drug release from PLGA microspheres after in vivo administration. The objective is to employ Förster resonance energy transfer (FRET) to visualize drug-encapsulated microspheres in both in vitro and in vivo settings. The primary goal is to establish a quantitative correlation between FRET fluorescence changes and microsphere drug release. The study selects drugs with diverse structures and lipid solubility to explore release mechanisms, using PLGA as the matrix material. Clozapine and risperidone serve as model drugs. FRET molecules, Cy5 and Cy5.5, along with Cy7 derivatives, create FRET donor–acceptor pairs. In vitro results show that FRET fluorescence changes align closely with microsphere drug release, particularly for the Cy5.5-Cy7 pair. In vivo experiments involve subcutaneous administration of microspheres to rats, tracking FRET fluorescence changes while collecting blood samples. Pharmacokinetic studies on clozapine and risperidone reveal in vivo absorption fractions using the Loo-Riegelman method. Correlating FRET and in vivo absorption data establishes an in vitro – in vivo relationship (IVIVR). The study demonstrates that FRET-based fluorescence changes quantitatively link to microsphere drug release, offering an innovative method for visualizing and monitoring release in both in vitro and in vivo settings, potentially advancing clinical applications of such formulations.
研究领域:
药剂学
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生物医学工程
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药理学
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产品关联
DOI
PubMed
高影响因子
NEUROPSYCHOBIOLOGY
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2023
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IF 3.2
Cao Ting,Wang LiWei,Jiao ShiMeng,Chen Hui,Lin ChenQuan,Zhang BiKui,Cai HuaLin
Introduction: Progesterone receptor component 1 (PGRMC1) has been identified as a potential target in atypical antipsychotic drug-induced metabolic disturbances as well as neuroprotection in the central nervous system. In our study, we aimed to figure out the essential role of PGRMC1 signaling pathway underlying clozapine-induced cognitive impairment. Methods: In male SD rats, we utilized recombinant adeno-associated viruses (BBB 2.0) and the specific inhibitor of PGRMC1 (AG205) to regulate the expression of PGRMC1 in the brain, with a special focus on the hippocampus. Treatments of clozapine and AG205 were conducted for 28 days, and subsequent behavioral tests including modified elevated plus maze and Morris water maze were conducted to evaluate the cognitive performance. Hippocampal protein expressions were measured by Western blotting. Results: Our study showed that long-term clozapine administration led to cognitive impairment as confirmed by behavioral tests as well as histopathological examination in the hippocampus. Clozapine inhibited neural survival through the PGRMC1/EGFR/GLP1R-PI3K-Akt signaling pathway, leading to a decrease in the downstream survival factor, brain-derived neurotrophic factor (BDNF), and simultaneously promoted neural apoptosis in the rat hippocampus. Intriguingly, by targeting at the hippocampal PGRMC1, we found that inhibiting PGRMC1 mimics, while its upregulation notably mitigates clozapine-induced cognitive impairment through PGRMC1 and its downstream signaling pathways. Conclusion: PGRMC1-overexpression could protect hippocampus-dependent cognitive impairment induced by clozapine. This effect appears to arise, in part, from the upregulated expression of PGRMC1/EGFR/GLP1R and the activation of downstream PI3K-Akt-BDNF and caspase-3 signaling pathways
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2024
·Vol. 47
·期 3
·2300745
·
IF 2.8
Jianhua Xiong,Linxin Tian,Xiantao Shen,Chuixiu Huang
Understanding and comparing the applicability of electromembrane extraction (EME) and liquid-phase microextraction (LPME) is crucial for selecting an appropriate microextraction approach. In this work, EME and LPME based on supported liquid membranes were compared using biological samples, including whole blood, urine, saliva, and liver tissue. After optimization, efficient EME and LPME of clozapine from four biological samples were achieved. EME provided higher recovery and faster mass transfer for blood and liver tissue than LPME. These advantages were attributed to the electric field disrupting clozapine binding to interfering substances. For urine and saliva, EME demonstrated similar recoveries while achieving faster mass transfer rates. Finally, efficient EME and LPME were validated and evaluated combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The coefficient of determination of all methods was greater than 0.999, and all methods showed acceptable reproducibility (≤14%), accuracy (90%–110%), and matrix effect (85%–112%). For liver and blood with high viscosity and complex matrices, EME-LC-MS/MS provided better sensitivity than LPME-LC-MS/MS. The above results indicated that both EME and LPME could be used to isolate non-polar basic drugs from different biological samples, although EME demonstrated higher recovery rates for liver tissue and blood.
研究领域:
分析化学
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药物分析
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生物医学工程
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jiajing Xin,Saihong Yan,Xiangsheng Hong,Huan Zhang,Jinmiao Zha
Clozapine (CLZ) is a neuroactive pharmaceutical that is frequently detected in aquatic environments. Although the cardiotoxicity, developmental toxicity, and neurotoxicity of CLZ in aquatic non-target organisms have been reported, its lipotoxicity and underlying mechanism are unknown. Therefore, in this study, 2-month-old Chinese rare minnows were exposed to 0, 0.1, 1, and 10 μg/L CLZ for 90 days. Overt dyslipidemia was observed after CLZ exposure, whereas the body weights of females significantly increased after CLZ exposure (p < 0.05). In addition, obvious hepatocyte vacuolization and hepatic lipid droplet accumulation were observed at all treatment groups (p < 0.05). The activities of sterol regulatory element binding proteins 1 (SREBP1) and fatty acid synthase (FAS) were significantly upregulated at the 1 and 10 μg/L CLZ treatment groups (p < 0.05). Moreover, evident cell boundary disintegration of the intestinal villi and increasing mucus secretion were observed at all treatment groups (p < 0.05). Furthermore, the diversity of the gut microbiota increased, whereas the relative abundances of Proteobacteria , Firmicutes and Bacteroidetes significantly increased after CLZ exposure (p < 0.05). Furthermore, significantly increased bacterial secondary bile acid biosynthesis activity in Chinese rare minnows was observed after 1 μg/L CLZ exposure (p < 0.05). Therefore, our findings confirmed that CLZ induced lipotoxicity by stimulating SREBP1 and affecting the bacterial secondary bile acid biosynthesis activity in Chinese rare minnows.
研究领域:
环境科学
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毒理学
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水生生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2020
·
IF 3.594
Kai Hu,Tiantian Pang,Yanmei Shi,Jiamin Cheng,Yanjie Huang
In this work, a facile strategy for the preparation of magnetic porous organic framework (Ni@POFs) was proposed by the reduction of Ni ions on its skeleton in situ. The properties of the material were confirmed by X-ray diffraction, vibrating sample magnetometer, infrared spectroscopy, transmission electron microscopy and scanning electron microscopy. The prepared Ni@POFs exhibits a strong magnetism and high extraction efficiency for targeted alkaloids. All the key factors that affect the extraction/desorption efficiency of the alkaloids onto the Ni@POFs material, such as sorbent amount, extraction time, sample pH and desorption condition, were investigated with the help of response surface methodology. In combination with magnetic solid phase extraction and ultra performance liquid chromatography-tandem mass spectrometry analysis, a novel method for the quantitative analysis of alkaloids in urine samples was proposed. The limits of detection and limits of quantitation for the eight alkaloids were found to be in the range of 0.9–6.0 and 3.0–20 pg mL −1 , respectively. The recoveries of spiked urine samples were in the range of 93.5–99.2% with RSDs less than 6.9%. The proposed method was successfully applied to analyze the metabolites in patient’s urine after the oral administration of berberine.
研究领域:
分析化学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）