Analytical Methods
·
2023
·Vol. 15
·期 33
·4179-4186
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IF 3.1
Xiaoxiao Li,Pan Chang,Xing Liu,Zhongjun Zhao,Wenwen Li,Yi Kang,Yixiang Duan,Wensheng Zhang
Ciprofol (HSK 3486, C14H20O), a novel 2,6-disubstituted phenol derivative similar to propofol, is a new type of intravenous general anaesthetic. We found that the exhaled ciprofol concentration could be measured online by ultraviolet time-of-flight mass spectrometry (UV-TOFMS), which could be used to predict the plasma concentration and anaesthetic effects of ciprofol. In this study, we present the calibration method and validation results of UV-TOFMS for the quantification of ciprofol gas. Using a self-developed gas generator to prepare different concentrations of ciprofol calibration gas, we found a linear correlation between the concentration and intensity of ciprofol from 0 parts per trillion by level (pptv) to 485.85 pptv (R2 = 0.9987). The limit of quantification was 48.59 pptv and the limit of detection was 7.83 pptv. The imprecision was 12.44% at 97.17 pptv and was 8.96% at 485.85 pptv. The carry-over duration was 120 seconds. In addition, we performed a continuous infusion of ciprofol in beagles, measured the exhaled concentration of ciprofol by UV-TOFMS, determined the plasma concentration by high-performance liquid chromatography, and monitored the anaesthetic effects as reflected by the bispectral index value. The results showed that the exhaled and plasma concentrations of ciprofol were linearly correlated. The exhaled ciprofol concentration correlated well with the anaesthetic effect. The study showed that we could use UV-TOFMS to provide a continuous measurement of gaseous ciprofol concentration at 20 second intervals.
研究领域:
药理学
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分析化学
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麻醉学
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产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 2
·106-117
·
IF 4.4
Yufan Zhou,Hongjiao Dong,Jiang Fan,Mingshe Zhu,Lu Liu,Yongbin Wang,Pingming Tang,Xiaoyan Chen
Ciprofol (HSK3486) is a novel intravenous agent for general anesthesia. In humans, HSK3486 mainly undergoes glucuronidation to form M4 [fraction of clearance (fCL): 62.6%], followed by the formation of monohydroxylated metabolites that further undergo glucuronidation and sulfation to produce M5-1, M5-2, M5-3, and M3 (summed fCL: 35.2%). However, the complete metabolic pathways of HSK3486 in humans remain unclear. In this study, by comparison with chemically synthesized reference standards, three monohydroxylated metabolites [M7-1, 4-hydroxylation with an unbound intrinsic clearance (CLint,u) of 2211 μl/min/mg; M7-2, ω-hydroxylation with a CLint,u of 600 μl/min/mg; and M7-3, (ω-1)-hydroxylation with a CLint,u of 78.4 μl/min/mg] were identified in human liver microsomes, and CYP2B6 primarily catalyzed their formation. In humans, M7-1 was shown to undergo glucuronidation at the 4-position and 1-position by multiple UDP-glucuronosyltransferases (UGTs) to produce M5-1 and M5-3, respectively, or was metabolized to M3 by cytosolic sulfotransferases. M7-2 was glucuronidated at the ω position by UGT1A9, 2B4, and 2B7 to form M5-2. UGT1A9 predominantly catalyzed the glucuronidation of HSK3486 (M4). The CLint,u values for M4 formation in human liver and kidney microsomes were 1028 and 3407 μl/min/mg, respectively. In vitro to in vivo extrapolation analysis suggested that renal glucuronidation contributed approximately 31.4% of the combined clearance. In addition to HSK3486 glucuronidation (M4), 4-hydroxylation (M7-1) was identified as another crucial oxidative metabolic pathway (fCL: 34.5%). Further attention should be paid to the impact of CYP2B6- and UGT1A9-mediated drug interactions and gene polymorphisms on the exposure and efficacy of HSK3486.
研究领域:
药理学
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生物化学
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临床医学
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DOI
PubMed
高影响因子
CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL
·
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 Integrative Neuroscience
·
2025
·Vol. 24
·期 8
·40079
·
IF 2.7
Jixin Chen,Guoyou Chen,Yueheng Wu,Shuai Liu,Yifan Ma,Maonan Liu,Wei Yu
Background and Purpose:Ciprofol, a novel intravenous anesthetic, has been shown to exert protective effects against ischemic stroke, a leading cause of death and disability; however, its molecular mechanisms remain unclear. This study aimed to explore the molecular mechanisms underlying the neuroprotective effects of ciprofol using metabolomics.Methods:This study used a middle cerebral artery occlusion (MCAO) rat model to simulate cerebral ischemia-reperfusion injury (CIRI). The rats were divided into ciprofol, MCAO, and sham groups. Histological and neurobehavioral testing methods were used to investigate the therapeutic effects of ciprofol in rats. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to screen for differential metabolites and related metabolic pathways in the serum and brain of the three groups. Spectrophotometry was used to detect in vitro mitochondrial respiratory chain complex I (MRCC-I) activity.Results:Neurological behavioral scores and cerebral infarct volumes of rats in the ciprofol group were significantly lower than those of rats in the MCAO group. Metabolomic analysis revealed 19 differential metabolites in serum samples and 31 differential metabolites in brain samples, including flavin mononucleotide (FMN). These metabolites were mainly enriched in the tricarboxylic acid cycle, respiratory electron transport chain, and amino acid and lipid metabolism. In vitro experiments demonstrated that ciprofol promoted the activity of MRCC-I during CIRI by increasing FMN levels.Conclusion:The mechanisms of action of ciprofol during treatment of cerebral ischemia involve the tricarboxylic acid cycle, respiratory electron transport chain, and amino acid and lipid metabolism and may directly affect MRCC-I activity by regulating FMN.
研究领域:
麻醉药理学
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神经生物学
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代谢组学
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线粒体功能
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脑血管病
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分子药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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