家兔唾液和尿液中氯胺酮浓度与血药浓度相关性研究

发布时间：2018-03-08 06:05

本文选题：氯胺酮　切入点：唾液　出处：《山西医科大学》2007年硕士论文　论文类型：学位论文

【摘要】： 目的建立急性中毒家兔唾液中氯胺酮及其代谢产物去甲氯胺酮的定性定量分析方法。研究灌胃组和静脉注射组家兔唾液和尿液中氯胺酮及去甲氯胺酮浓度与血药浓度的相关性。方法唾液样品分析方法:急性中毒家兔分为毛果芸香碱刺激组和非刺激组,于给药后不同时间点无菌唾液收集管收集唾液,t检验比较研究两组氯胺酮和去甲氯胺酮检出量有无显著性差异。唾液样品中加入内标物SKF_(525A)后碱化,乙酸乙酯萃取,气相色谱/质谱联用(GC/MS)全扫描定性,气相色谱(GC)定量分析。相关性研究:家兔以半数致死量(LD_(50))分别灌服和静脉注射氯胺酮,给药后不同时间点收集血液、唾液及尿液标本(颈动脉采血,分离血浆;无菌唾液收集管收集唾液;导尿管收集尿液),GC法测定各时间点药物浓度,采用双变量Pearson相关分析研究唾液和血液、血液和尿液间氯胺酮及去甲氯胺酮浓度的相关性。结果1.建立了唾液中氯胺酮及其代谢产物去甲氯胺酮的定性定量分析方法。氯胺酮及去甲氯胺酮在唾液中检测线性范围为0.01～101μg·mL~(-1),最低检出限均为0.005μg·mL~(-1),方法回收率为95.03%～105.35%,RSD均小于10%。对于同一时间点毛果芸香碱刺激组和非刺激组之间氯胺酮和去甲氯胺酮在唾液中的检出量无显著性差异(P＞0.05)。2.灌胃组给药后各时间点氯胺酮及去甲氯胺酮在唾液和血液中的浓度均有相关性,相关系数r达到高度相关水平,分别在0.88～0.95,0.86～0.96之间,平均为0.912和0.914,30～60min相关度最好;静脉注射组氯胺酮及去甲氯胺酮唾液和血液中的浓度也有良好的相关性,相关系数r分别在0.8～0.96,0.86～0.95之间,平均为0.899和0.912。两实验组氯胺酮及去甲氯胺酮在血液和尿液中的浓度也存在相关性,灌胃组于给药后240min内达到中度相关水平,平均为0.596和0.606,给药240min后r值低于0.5;静脉注射组180min内氯胺酮及去甲氯胺酮在血液和尿液的相关系数r均达到中度相关水平,平均为0.615和0.620,给药180min后r值低于0.5。结论1.建立的急性中毒家兔唾液收集和唾液中氯胺酮及去甲氯胺酮的分析方法简便、灵敏、快捷,适用于氯胺酮中毒与滥用案例唾液的快速检验鉴定。用毛果芸香碱刺激唾液的分泌,不会影响唾液中药物的浓度,可用于唾液的分析研究。2.灌胃组和静脉注射组唾液和血液之间均存在很好的相关性,血液和尿液分别在240min和180min内存在中度相关性,之后随时间变化r值小于0.5。因此唾液可作为氯胺酮滥用案件的生物检材,可根据唾液药物浓度推断血药浓度,并用于法医学案件的鉴定分析和临床药物监测。与唾液和血液相比,氯胺酮在家兔尿液和血液中的相关度较差,尿液中药物浓度并不能直接反映血药浓度,因此用尿液药物浓度推断血药浓度时应谨慎考虑。
[Abstract]:Objective to establish a qualitative and quantitative method for the determination of ketamine and its metabolite in saliva of rabbits with acute poisoning, and to study the correlation between the concentration of ketamine and norketamine in saliva and urine and the concentration of norketamine in saliva and urine of rabbits in gastric perfusion group and intravenous injection group. Methods: acute poisoning rabbits were divided into pilocarpine stimulation group and non-stimulation group. A comparative study on the detection of ketamine and norketamine in saliva collected by sterile saliva collection tube at different time points after administration. The saliva samples were alkalized and extracted with ethyl acetate after the addition of the internal standard SKFStug 525A. Gas Chromatography / Mass Spectrometry (GC / MS) combined with GC / MS for qualitative Analysis and Gas Chromatography (GC / MS) quantitative Analysis. Correlation study: rabbits were given Ketamine by 50% lethal dose and ketamine was injected intravenously, and blood was collected at different time points after administration. Saliva and urine samples (carotid artery blood collection, plasma separation; aseptic saliva collection tube to collect saliva; urinary catheter collection urine and GC method to determine the drug concentration at all time points, using bivariate Pearson correlation analysis to study saliva and blood, Correlation between blood and urine concentrations of m-ketamine and norketamine. Results 1. A qualitative and quantitative method for the determination of ketamine and its metabolite in saliva was established. The linear range of ketamine and norketamine in saliva was 0.01 渭 g 路mL ~ (-1), the lowest detection limit was 0.005 渭 g 路mL ~ (-1), and the recovery rate was 95.03 ~ 105.35 RSD. There was no significant difference in the detection of ketamine and norketamine in saliva between pilocarpine stimulation group and non-stimulation group at the same time point (P > 0.05). There is a correlation between saliva and blood concentrations, The correlation coefficient (r) reached a high correlation level between 0.88 ~ 0.95 ~ 0.86 ~ 0.96, with an average correlation of 0.912 and 0.914 ~ 30 ~ (60) min. There was also a good correlation between the saliva and blood concentrations of ketamine and norketamine in intravenous injection group, and the correlation coefficient r was between 0.80.96 and 0.860.95, respectively, in intravenous injection group, the correlation coefficient was between 0.86 and 0.86 0.95, and there was a good correlation between the concentrations of ketamine and norketamine in saliva and blood in intravenous injection group. The concentrations of ketamine and norketamine in blood and urine of the two experimental groups were also correlated, and the levels of ketamine and norketamine in the gavage group reached a moderate level within 240 minutes after administration. The mean values of Ketamine and norketamine in blood and urine were 0.596 and 0.606, respectively, and the correlation coefficients of ketamine and norketamine in blood and urine reached moderate correlation level within 180 min after injection, the average values were 0.615 and 0.620, and the r values were lower than 0.5 after 180 minutes of administration. Conclusion 1. The method for the collection of saliva and the determination of ketamine and norketamine in saliva of rabbits with acute poisoning was simple, sensitive and rapid. Suitable for rapid detection and identification of saliva in cases of ketamine poisoning and abuse. Stimulating saliva secretion with pilocarpine does not affect the concentration of drugs in saliva. There was a good correlation between saliva and blood in gavage group and intravenous injection group, and there was a moderate correlation between blood and urine in 240 min and 180 min, respectively. Then the value of r is less than 0.5 over time. Therefore, saliva can be used as a biological sample of ketamine abuse cases, and the blood drug concentration can be inferred from the concentration of saliva drugs. Compared with saliva and blood, ketamine is less correlated in urine and blood of rabbits, and the concentration of ketamine in urine can not directly reflect the concentration of drugs in blood. Therefore, careful consideration should be given to the estimation of blood drug concentration by urine drug concentration.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：D919

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