本文選題：氯胺酮　切入點：唾液　出處：《山西醫(yī)科大學(xué)》2007年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的建立急性中毒家兔唾液中氯胺酮及其代謝產(chǎn)物去甲氯胺酮的定性定量分析方法。研究灌胃組和靜脈注射組家兔唾液和尿液中氯胺酮及去甲氯胺酮濃度與血藥濃度的相關(guān)性。 方法唾液樣品分析方法:急性中毒家兔分為毛果蕓香堿刺激組和非刺激組,于給藥后不同時間點無菌唾液收集管收集唾液,t檢驗比較研究兩組氯胺酮和去甲氯胺酮檢出量有無顯著性差異。唾液樣品中加入內(nèi)標(biāo)物SKF_(525A)后堿化,乙酸乙酯萃取,氣相色譜/質(zhì)譜聯(lián)用(GC/MS)全掃描定性,氣相色譜(GC)定量分析。相關(guān)性研究:家兔以半數(shù)致死量(LD_(50))分別灌服和靜脈注射氯胺酮,給藥后不同時間點收集血液、唾液及尿液標(biāo)本(頸動脈采血,分離血漿;無菌唾液收集管收集唾液;導(dǎo)尿管收集尿液),GC法測定各時間點藥物濃度,采用雙變量Pearson相關(guān)分析研究唾液和血液、血液和尿液間氯胺酮及去甲氯胺酮濃度的相關(guān)性。 結(jié)果1.建立了唾液中氯胺酮及其代謝產(chǎn)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檢測線性范圍為0.01～101μg·mL~(-1),最低檢出限均為0.005μg·mL~(-1),方法回收率為95.03%～105.35%,RSD均小于10%。對于同一時間點毛果蕓香堿刺激組和非刺激組之間氯胺酮和去甲氯胺酮在唾液中的檢出量無顯著性差異(P＞0.05)。2.灌胃組給藥后各時間點氯胺酮及去甲氯胺酮在唾液和血液中的濃度均有相關(guān)性,相關(guān)系數(shù)r達(dá)到高度相關(guān)水平,分別在0.88～0.95,0.86～0.96之間,平均為0.912和0.914,30～60min相關(guān)度最好;靜脈注射組氯胺酮及去甲氯胺酮唾液和血液中的濃度也有良好的相關(guān)性,相關(guān)系數(shù)r分別在0.8～0.96,0.86～0.95之間,平均為0.899和0.912。兩實驗組氯胺酮及去甲氯胺酮在血液和尿液中的濃度也存在相關(guān)性,灌胃組于給藥后240min內(nèi)達(dá)到中度相關(guān)水平,平均為0.596和0.606,給藥240min后r值低于0.5;靜脈注射組180min內(nèi)氯胺酮及去甲氯胺酮在血液和尿液的相關(guān)系數(shù)r均達(dá)到中度相關(guān)水平,平均為0.615和0.620,給藥180min后r值低于0.5。 結(jié)論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簡便、靈敏、快捷,適用于氯胺酮中毒與濫用案例唾液的快速檢驗鑒定。用毛果蕓香堿刺激唾液的分泌,不會影響唾液中藥物的濃度,可用于唾液的分析研究。2.灌胃組和靜脈注射組唾液和血液之間均存在很好的相關(guān)性,血液和尿液分別在240min和180min內(nèi)存在中度相關(guān)性,之后隨時間變化r值小于0.5。因此唾液可作為氯胺酮濫用案件的生物檢材,可根據(jù)唾液藥物濃度推斷血藥濃度,并用于法醫(yī)學(xué)案件的鑒定分析和臨床藥物監(jiān)測。與唾液和血液相比,氯胺酮在家兔尿液和血液中的相關(guān)度較差,尿液中藥物濃度并不能直接反映血藥濃度,因此用尿液藥物濃度推斷血藥濃度時應(yīng)謹(jǐn)慎考慮。
[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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：D919

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