MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Xiao Li,Xuanwei Li,Caixia Yan,Yaokun Xia,Keke Huang,Jia Chen
Alkyl carboxylic acid–HFIP SUPRAS was developed as an ideal extractant for HF-LPME. • Reversed micellar SUPRAS forms with low HFIP and is stable at low salt levels. • Hollow fiber and restricted-access SUPRAS synergistically reduce matrix effects. • Multiclass antiarrhythmic drugs in human plasma are detected by LC-MS/MS. • Low solvent/sample consumption and an AGREEprep score of 0.5 ensure eco-friendliness. An alkyl carboxylic acid–hexafluoroisopropanol (HFIP) supramolecular solvent (SUPRAS) was developed as a restricted-access solvent for hollow fiber liquid-phase microextraction (HF-LPME) and applied to the determination of seven antiarrhythmic drugs (mexiletine, propranolol, diltiazem, amlodipine, propafenone, verapamil, and amiodarone) in human plasma. SUPRAS formation required only a low HFIP dosage (<10%, v /v for alkyl carboxylic acid ≤4%, w / v ) and was minimally affected by low ionic strength (NaCl <50 mM) or low organic solvent content (methanol <5%, v /v). The SUPRAS consisted of reversed micellar aggregates with hydrophobic outer surfaces and hydrophilic inner cavities. The SUPRAS exhibited restricted-access behavior, efficiently excluding macromolecular proteins (extraction efficiency <18.3%, solubility <4.5 mg mL −1 ) via the synergistic effects of protein denaturation/flocculation induced by HFIP and octanoic acid and size exclusion by the SUPRAS matrix. After systematic optimization, the proposed method coupled with high-performance liquid chromatography-tandem mass spectrometry demonstrated acceptable analytical performance. Satisfactory linearity was achieved, with correlation coefficients ranging from 0.9903 to 0.9997. Method limits of detection (S/N = 3) ranged from 0.01 to 0.10 μg L −1 , while method limits of quantification (S/ N = 10) were 0.03–0.33 μg L −1 . Acceptable recoveries were obtained for spiked samples (86.5–126.6%), with only two analytes slightly exceeding 130% at the low concentration level, and intra- and inter-day precisions were below 19.3%. Owing to the combined microfiltration capability of the hollow fiber and the restricted-access properties of the SUPRAS, the method exhibited manageable matrix effects (70.6–132.5%) and eliminated the need for a separate protein precipitation step, while consuming only 25 μL of SUPRAS per extraction. Greenness assessment using AGREEprep software yielded a score of 0.5, confirming satisfactory eco-friendliness and sustainability. This SUPRAS-HF-LPME method is simple, efficient, and environmentally benign, serving as a promising pretreatment and quantification strategy for antiarrhythmic drugs in complex human plasma matrices. Download: Download high-res image (265KB) Download: Download full-size image
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Wang Yiran,Shi Jihua,Dai Dapeng,Cai Jianping,Wang Shuanghu,Hong Yun,Zhou Shan,Zhao Fangling,Zhou Quan,Geng Peiwu,Zhou Yunfang,Xu Xue,Luo Qingfeng
As a novel acid-suppressing drug, vonoprazan shows the potential to replace traditional proton-pump inhibitors. With its widespread use, some adverse effects that require further study have emerged due to drug–drug interactions. Our study is the first experiment that evaluated the drug–drug interactions of eleven common cardiovascular drugs that inhibit vonoprazan metabolism in vitro and in vivo. Rat liver microsome incubation and molecular simulation docking were applied to explore the inhibition mechanism. Amlodipine and nifedipine showed inhibitory effects on vonoprazan metabolism in both rat and human liver microsomes in the first evaluation part in vitro. The inhibition mechanism analysis results demonstrated that amlodipine and nifedipine might inhibit the metabolism of vonoprazan by a mixed type of competitive and non-competitive inhibition. However, the pharmacokinetic data of the vonoprazan prototype revealed that amlodipine affected vonoprazan in vivo while nifedipine did not. Thus, more attention should be paid when amlodipine is prescribed with vonoprazan. Furthermore, the changes in its carboxylic acid metabolites MI hinted at a complex situation. Molecular simulation suggested the CYP2B6 enzyme may contribute more to this than CYP3A4, and further inhibitory experiments preliminarily verified this speculation. In conclusion, the use of vonoprazan with cardiovascular drugs, especially amlodipine, should receive particular attention in clinical prescriptions.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Lanteng Wang,Jin Wang,Ang Zhang,Xin-an Huang,Hongtao Lei
A growing number of β -agonists are illegally using for reducing animal fat deposition in animals, but the development of analytical methods always lags behind the emergence of new illegal compounds. Therefore, class specificity antibody-based immunoassays that can detect a great many β -agonists are important for timely supervision. In this study, a competitive inhibition enzyme-linked immunosorbent assay (ciELISA) based on a clenbuterol monoclonal antibody was developed to recognize 23 β -agonists and analogues. Holographic and three-dimensional quantitative structure–activity relationship (HQSAR and 3D QSAR) revealed that there are two critical binding epitopes on β -agonist hapten affecting antibody specificity, and these epitopes have been further validated using a ractopamine antibody with narrow specificity. Tert -butyl at C-2′ epitope is needed to generate class specific antibodies, and different characteristics of substituents at benzene ring epitope would adjust antibody specificity. This investigation could provide reference for future design of β -agonist haptens.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 12
·期 2
·141-148
·
IF 2.378
Xue Ren,Man He,Beibei Chen,Bin Hu
Herein, magnetic porous organic polymers (MOPs) prepared via an azo coupling reaction in water under mild conditions are evaluated for the extraction of seven cardiovascular drugs, including xylocaine, metoprolol, mexiletine, labetalol, propranolol, carvedilol and propafenone, from human urine samples for the first time. The extraction mechanisms are assumed to be electrostatic interaction and π–π stacking. The MOPs exhibited fast adsorption/desorption time (13 min) and high enrichment factors (315–365-fold) for target analytes. Based on this, a method coupling magnetic solid phase extraction with HPLC-UV detection was developed for the analysis of cardiovascular drugs. Under the optimized conditions, the LODs (S/N = 3) were in the range of 0.06–0.57 μg L−1 with an RSD (n = 5) of 4.3–8.6%, and the linear range was 0.2–200 μg L−1 for propranolol, 2–200 μg L−1 for metoprolol, and 0.5–200 μg L−1 for the other five analytes. The developed method was applied for the analysis of cardiovascular drugs in urine samples with recoveries of 89.0–112%. In order to further evaluate the application potential of this method, real-time monitoring of metoprolol in urine samples collected from volunteers treated with metoprolol tablets was performed. The proposed method is simple, fast, and sensitive and has good potential in the monitoring of cardiovascular drugs in competitive sports and clinical analysis.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2016
·
IF 3.926
Wenying Fan,Man He,Linna You,Xuewei Zhu,Beibei Chen,Bin Hu
Due to the high selectivity and stability, molecularly imprinted polymers (MIPs) have been successfully applied in stir bar sorptive extraction (SBSE) as a special coating to improve the selective extraction capability for target analytes. However, traditional MIPs usually suffer from incompatibility in aqueous media and low adsorption capacity, which limit the application of MIP coated stir bar in aqueous samples. To solve these problems, a water-compatible graphene oxides (GO)/MIP composite coated stir bar was prepared in this work by in situ polymerization. The prepared water-compatible GO/MIP coated stir bar presented good mechanical strength and chemical stability, and its recognition ability in aqueous samples was improved due to the polymerization of MIP in water environment, the adsorption capacity for target analytes was also increased by the addition of GO in MIP pre-polymer solution. Based on it, a method of water-compatible GO/MIP coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detector (HPLV-UV) was proposed for the analysis of propranolol (PRO) in aqueous solution. The influencing factors of SBSE, such as sample pH, salt effect, stirring rate, extraction time, desorption solvent and desorption time, were optimized, and the analytical performance of the developed SBSE-HPLC-UV method was evaluated under the optimized conditions. The limit of detection (LOD) of the proposed method for PRO was about 0.37 μg L −1 , and the enrichment factor (EF) was 59.7-fold (theoretical EF was 100-fold). The reproducibility was also investigated at concentrations of 5 μg L −1 and the relative standard deviation (RSD) was found to be 7.3% (n = 7). The proposed method of GO/MIP coating-SBSE-HPLC-UV was successfully applied for the assay of the interested PRO drug in urine samples, and further extended to the investigation of the excretion of the drugs by monitoring the variation of the concentration of PRO in urine within 10 h after drug-taking.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Chang Di,Tong Wu,Kai Gao,Na Li,Huifang Song,Lili Wang,Haojie Sun,Jingyun Yi,Xinran Zhang,Jiexin Chen,Mala Shah,Yuwu Jiang,Zhuo Huang
Background and Purpose KCNT1 encodes a sodium-activated potassium channel (Slack channel), and its mutation can cause several forms of epilepsy. Traditional antiepileptic medications have limited efficacy in treating patients with KCNT1 mutations. Here, we describe one heterozygous KCNT1 mutation, M267T, in a patient with EIMFS. The pathological channel properties of this mutation and its effect on neuronal excitability were investigated. Additionally, this study aimed to develop a medication for effective prevention of KCNT1 mutation-induced seizures. Experimental Approach Wild-type or mutant KCNT1 plasmids were expressed heterologously in Xenopus laevis oocytes, and channel property assessment and drug screening were performed based on two-electrode voltage-clamp recordings. The single-channel properties were investigated using the excised inside-out patches from HEK293T cells. Through in utero electroporation, WT and M267T Slack channels were expressed in the hippocampal CA1 pyramidal neurons in male mice, followed by the examination of the electrical properties using the whole-cell current-clamp technique. The kainic acid-induced epilepsy model in male mice was used to evalute the antiseizure effects of carvedilol. Key Results The KCNT1 M267T mutation enhanced Slack channel function by increasing single-channel open probability. Through screening 16 FDA-approved ion channel blockers, we found that carvedilol effectively reversed the mutation-induced gain-of-function channel properties. Notably, the KCNT1 M267T mutation in the mouse hippocampal CA1 pyramidal neurons affected afterhyperpolarization properties and induced neuronal hyperexcitability, which was inhibited by carvedilol. Additionally, carvedilol exhibited antiseizure effects in the kainic acid-induced epilepsy model. Conclusion and Implication Our findings suggest carvedilol as a new potential candidate for treatment of epilepsies. Graphical
✓ 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）