JOURNAL OF WATER AND HEALTH
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2024
·Vol. 22
·期 5
·887-895
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IF 2.5
Yuan Shuai,Xiao Yue,Luo Ruxin,Wang Xin,Xiang Ping
Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography–tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples ( n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements. Etomidate (ET) use has spread rapidly, and it is now one of the most seriously abused substances in China. Our study first developed a simple, fast, and sensitive direct injection method for the quantitative determination of ET and etomidate acid in wastewater. After optimizing the UPLC–MS/MS and sample pretreatment conditions, the method was applied to authentic wastewater samples ( n = 245) from several WWTPs in China.
研究领域:
分析化学
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环境科学
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药物滥用研究
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 6
·805
·
IF 4.9
Ailing Wu,Houyin Shi,Luhan Yang,Hao Zhang,Xichen Nan,Dan Zhang,Zhuo Zhang,Chun Zhang,Siwei Chen,Xiujuan Fu,Lilan Ou,Lulu Wang,Yanyan Shi,Hao Liu
Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.
研究领域:
药剂学
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神经科学
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临床医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2018
·
IF 2.297
Hao Liu,Xuemei Zhou,Yingying Wang,Menglu Yang,Xiaohui Xu,Ailing Wu
Etomidate is one of the first-line general anesthetic agents , with distinguished properties such as rapid onset, excellent cardiovascular stability, minimal impact on respiratory system, etc . However, the clinical application of etomidate preparation is often confined by the notable defects of both the drug and its current formulations. Previously, we reported a new etomidate formulation based on Pluronic F108 micelle which demonstrated improved anesthetic effects. Nevertheless, the micellar encapsulation of etomidate was limited using only one kind of Pluronic, which required organic solvents to modulate the hydrophobicity . Besides, the biocompatibility of this formulation was not yet clear. Herein, we reported that mixed nanomicelles consisting of different Pluronic could make full advantage of each loading material, which led to improved physicochemical properties for the delivery of etomidate. Moreover, in vivo studies demonstrated that, the etomidate-loaded mixed micelle (Eto-PFM) maintained the anesthetic effects and rapid onset property of etomidate, with a broad safe dose range. The potential mechanisms of the acute toxicity were also discussed. The results suggest that Eto-PFM is a promising etomidate preparation with the potential to further develop as an alternative to the current etomidate preparations.
研究领域:
药剂学
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生物医学工程
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毒理学
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DOI
高影响因子
Toxicologie Analytique et Clinique
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2025
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IF 1.7
Xiaolong Zhang,Kundi Zhao,Yuxuan Chen,Jinlei Liu,Jie Gu,Mengchao Wang,Yinyin Dai,Huimin Zhang,Amin Wurita,Koutaro Hasegawa
Summary Introduction Distribution of imidazole-derived GABA agonists, such as etomidate, metomidate and its analogs have been encountered frequently especially in China, along with its abuse cases. Recently, we were enquired to investigate urine samples and dubious powder seized from abuse cases, in which a new etomidate analog isopropoxate was detected. Methods The etomidate analog contained in the seized powder was tried to be identified using gas chromatography-mass spectrometry and by hydrolysis its ester structure to related alcohol under basic reaction environment, as a preliminary analysis for the powder composition. Reference standard were then purchased to identify the compound in suspected powder. For urine samples, after adding the internal standard and acetonitrile to the urine samples followed by vortexing and centrifugation, the supernatant layer was analyzed by LC-MS/MS. Results For LC-MS/MS analysis, the coefficient of determination (r2) values of the calibration curves of etomidate acid and isopropoxate in the urine were more than 0.99; the limits of detection (LODs) for etomidate acid, and isopropoxate was 0.025 ng/mL; the limits of quantification (LOQs) of them was 0.05 ng/mL. Etomidate acid and isopropoxate could be determined from submitted urines. And nine isopropoxate metabolites and their major metabolic pathways were identified. Conclusions In this study, we have established a simultaneous and reliable analytical method for etomidate acid and isopropoxate in human urine by LC-MS/MS, and the method could be applied to authentic cases. It is also the first time that the metabolic pathway of isopropoxate in the human body has been explored.
研究领域:
毒理学
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分析化学
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法医学
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产品关联
DOI
高影响因子
Nanomaterials
·
2024
·Vol. 14
·期 23
·1958
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IF 4.4
Yan Mo,Xiaoping Zhang,Ke Zou,Wen Xing,Xiayang Hou,Yu Zeng,Yugang Cai,Ruixiang Xu,Hongwen Zhang,Weiping Cai
Etomidate (ET), a medical anesthetic, is increasingly being incorporated into e-liquids for consumption and abuse as a new psychoactive substance (NPS), leading to significant social issues. In this work, large-area Au micro- and nano-structured ordered arrays were engineered as surface-enhanced Raman spectroscopy (SERS) substrates for fast detection and precise identification of ET and its metabolites. This ordered array, characterized by abundant electromagnetic enhancement hotspots and structural uniformity, imparts unique properties to the SERS substrate, including ultra-sensitivity, spectral signal reproducibility, and precise quantitative capabilities. Furthermore, it effectively mitigates interference from the complex matrix of e-liquids, facilitating the rapid detection of trace amounts of ET molecules. This SERS rapid detection technology can act as a preliminary screening method for gold-standard spectroscopic analysis, facilitating the on-site rapid screening of suspicious samples and thereby enabling efficient detection and precise verification.
研究领域:
分析化学
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医学
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材料科学
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DOI
PubMed
高影响因子
CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL
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2025
·
IF 1.5
Linzhong Zhang,Lingchun Kong,Qi Deng,Yukai Chao,Chibing Fu,Yutong Meng
Objective To evaluate the physical and chemical compatibility and stability of a cipepofol (ciprofol) and etomidate (EC) mixture for intravenous anesthesia and assess the physiochemical stability of the drugs during co-administration through the same intravenous line. Methods High-performance liquid chromatography and other analytical techniques were employed to investigate the stability of the EC mixture. The mixture was prepared and stored at 4, 25, or 37°C for 24 h, and its appearance, pH, osmotic pressure, particle size, zeta potential, drug content, and related substances were evaluated at 0, 1, 3, 6, 12, and 24 h. Results The EC mixture maintained physical stability, with no significant changes in appearance, pH (fluctuation, ≤0.07 units), osmotic pressure (relative standard deviation [RSD] < 2.0%), or particle size observed over 24 h. Zeta potential remained within acceptable limits (ranging from −40 to −30 mV), indicating good colloidal stability. Chemically, drug content remained at ≥99.9% of the initial level (RSD < 1.2%), and impurity levels stayed within the specified limits (maximum single impurity ≤ 0.13%, total impurities ≤ 0.37%). Conclusion The findings suggest that the EC mixture was physically and chemically compatible and stable for up to 24 h at various temperatures, making this regimen a potentially safe and effective option for intravenous anesthesia. This finding is significant for improving patient comfort and reducing adverse drug reactions during anesthesia induction and maintenance.
研究领域:
药理学
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麻醉学
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药物化学
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2018
·
IF 2.297
Ailing Wu,Yingying Wang,Su Min,Hao Liu,Fei Xie
Etomidate is one of the most commonly used intravenous ( i.v. ) general anesthetics with rapid onset, minimal impact on breathing and excellent hemodynamic stability. But its application is usually coupled with several disadvantages including inadequate water-solubility for injection and adrenal toxicity in particular. Selective delivery of etomidate to brain via some water-soluble nanocarriers provides a potential way to settle these problems. In this study, etomidate-loaded poloxamer micelles (Eto-SOPM) were prepared using a thin-film hydration method. Soybean oil (SO) was used to enhance the encapsulation of etomidate, which resulted in acceptable drug concentration (2 mg/mL) for injection. The drug release of Eto-SOPM was not significantly hindered by encapsulation or the addition of soybean oil, and was faster than that of the commercially available etomidate fat emulsion (P < 0.001). The in vivo study revealed that the drug potency of etomidate was not significantly affected by encapsulation, and that Eto-SOPM had notably shortened action period as compared with etomidate fat emulsion (P < 0.001). As rapid onset and short action period are two essential requirements of general anesthetics, these results suggested that Eto-SOPM represents a promising etomidate preparation for short-acting general anesthesia and warrants more study in the future.
研究领域:
药剂学
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麻醉学
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生物医学工程
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
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2023
·
IF 5.6
Hao Liu,Jing-Kun Miao,Meng Cai,Lin Gan,Hui-Qing Zhao,Xiao-Feng Lei,Jin Yu
Objective: This study aims to determine the drug concentration of etomidate, remifentanil, and rocuronium bromide for general anesthesia in fetus as well as the placental transport rate between term and preterm delivery, twins, and singleton. Study design: Sixty parturients with 72 fetuses undergoing cesarean section under general anesthesia were included. According to whether the fetus was a twin or premature, parturients were divided into Group I (term singleton), Group II (premature singleton), Group III (term twins), and Group IV (premature twins). The preoperative demographic characteristics and laboratory examination of parturients, hemodynamic indicators, the Apgar score of neonates at 1, 5, and 10 min after delivery and at specific assigned values, umbilical artery blood gas analysis results, neonatal weight, and resuscitative measures were recorded. Anesthetic drug concentrations in maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood were detected by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Result: No significant differences were observed in the concentrations of etomidate, remifentanil, and rocuronium bromide in MA, UV, and UA blood, or in the UV/MA and UA/UV ratios between term and preterm infants, twins, and singletons. Moreover, there was no variation in the anesthetic drug concentration among each pair of twins. Additionally, no correlation was found between the neonatal weight and the plasma concentrations of anesthetic drugs in UV and UA blood, except for remifentanil in UA blood. Conclusion: Preterm or twin deliveries do not affect the neonatal concentration of etomidate, remifentanil, and rocuronium bromide used in general anesthesia for cesarean sections. Clinical Trial Registration: www.chictr.org.cn , identifier ChiCTR2100046547
研究领域:
妇产科学
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麻醉学
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药理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-8
·
IF 3.9
Liu Hao,Cai Meng,Peng Yong,Miao Jing-kun,Yu Jin
While remifentanil, etomidate, and rocuronium are increasingly used for cesarean section due to their favorable hemodynamic stability and fetal safety profile, their pharmacokinetics and potential effects on neonates remain poorly understood. This study developed and validated a rapid, sensitive LC–MS/MS method for simultaneous quantification of the three anesthetics in microsamples of 10 μl serum, followed by a paired maternal and umbilical cord serum investigation. After protein precipitation with acetonitrile, analytes were separated within 4 min using positive electrospray ionization in MRM mode. Method validation demonstrated excellent linearity (R 2 > 0.99) for all compounds, with LLOQs of 0.15 ± 0.02 ng/mL (remifentanil), 16.87 ± 0.51 ng/mL (etomidate), and 106.73 ± 8.63 ng/mL (rocuronium). Precision (intra-/inter-day < 15%) and minimal carry-over (< 5%) met bioanalytical standards. Applied to 20 maternal-newborn pairs, the method quantified differential drug distribution: maternal arterial concentrations (remifentanil 4.75 ± 0.19 ng/mL; etomidate 412.71 ± 35.29 ng/mL; rocuronium 7.08 ± 0.48 μg/mL) exceeded umbilical vein levels (2.43 ± 0.13 ng/mL; 302.15 ± 29.03 ng/mL; 0.86 ± 0.16 μg/mL), which were higher than umbilical artery concentrations (1.33 ± 0.15 ng/mL; 166.24 ± 21.53 ng/mL; 0.44 ± 0.77 μg/mL). Calculated placental transfer rates significantly differed among anesthetics (remifentanil 0.52 ± 0.02; etomidate 0.75 ± 0.04; rocuronium 0.13 ± 0.02; all P < 0.001), reflecting distinct pharmacokinetic behaviors. The validated method enables reliable microvolume analysis for perinatal pharmacokinetic studies, particularly valuable when sample availability is limited. Its rapid throughput and sensitivity make it suitable for clinical research applications investigating maternal–fetal drug transfer dynamics.
研究领域:
分析化学
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药代动力学
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麻醉学
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妇产科学
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新生儿学
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临床研究
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产品关联
DOI
PubMed
高影响因子
FORENSIC SCIENCE INTERNATIONAL
·
2024
·
IF 2.2
Jiahao Li,Jiang Ling,Zihao Cai,Yingyuan Liao,Ping Xiang,Wenlong Liu,Yanjun Ding
Etomidate as a non-barbiturate sedative, has central inhibitory effect and addiction and has been listed as a controlled drug in some countries due to the abusing trend nowadays. Therefore, rapid and sensitive detection of etomidate is of great significance. In this work, a novel fluorescent sensing probe (CuNCs@MIPs) based on copper nanoclusters (CuNCs) and molecular imprinted polymers (MIPs) has been firstly reported. CuNCs was environment-friendly synthesized using poly(vinylpyrrolidone) as a template and ascorbic acid as a reducing agent. After functionalized with molecular imprinting technique, the CuNCs@MIPs probe has special binding cavities on surface to target etomidate, causing the fluorescence intensity rapidly decrease, which confirmed it has excellent sensitivity, selectivity and stability. Under optimal conditions, the fluorescent sensing probe presented high precision linear relationship for etomidate in range of 10–500 ng/ml with detection limit of 10 ng/ml, and the whole detection process was completed within 10 min. This sensing method has also been applied to real samples detection, still demonstrated excellent feasibility in electronic cigarette liquids and urine. More importantly, compared with previous methods, this fluorescent sensing method has advantages such as rapid, simple and easy to operate. Collectively, the proposed CuNCs@MIPs sensing probe has good fluorescence characteristics and simple synthesis strategy, showed a great potential in etomidate detection and application.
研究领域:
分析化学
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纳米技术
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药物检测
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荧光传感
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DOI
高影响因子
危险品化学品经营许可证（带存储）