發(fā)布時(shí)間：2018-05-27 20:05

  本文選題：甲基苯丙胺 + 乙醇��； 參考：《山西醫(yī)科大學(xué)》2005年碩士論文

【摘要】：目的:1、建立生物樣品中甲基苯丙胺及其主要活性代謝產(chǎn)物苯丙胺的GC/MS 定性定量分析方法。2、比較研究單用甲基苯丙胺與合用乙醇后的甲基苯丙胺在家兔體內(nèi)的毒代動(dòng)力學(xué)過(guò)程。3、觀察實(shí)驗(yàn)動(dòng)物給藥前和給藥后生命體征的動(dòng)態(tài)變化規(guī)律。 方法:1、氣相色譜/質(zhì)譜聯(lián)用(GC/MS)檢測(cè)方法:血清、尿液樣品中加入內(nèi)標(biāo)物SKF525A后堿化,乙醚萃取,TFA 衍生化,GC/MS 全掃描定性,選擇離子掃描(SIM)定量分析。2、毒代動(dòng)力學(xué)研究:單用甲基苯丙胺組以15mg·kg~(-1)劑量灌服甲基苯丙胺,合用乙醇組先以3g·kg~(-1)乙醇灌胃,再灌服甲基苯丙胺(15 mg·kg~(-1))。分別于給藥前和給藥后不同時(shí)間點(diǎn)收集血尿標(biāo)本(頸動(dòng)脈采血,分離血清;導(dǎo)尿管收集尿液),用GC/MS 方法測(cè)定各時(shí)間點(diǎn)藥物濃度。采用3P97 程序進(jìn)行房室模型擬合以及毒代動(dòng)力學(xué)參數(shù)計(jì)算。3、生命體征監(jiān)測(cè):BL-5 生理機(jī)能實(shí)驗(yàn)系統(tǒng)全程記錄實(shí)驗(yàn)動(dòng)物的心電、血壓和呼吸等主要生命體征變化。 結(jié)果:1、GC/MS 法檢測(cè)血清和尿液中甲基苯丙胺與苯丙胺的線(xiàn)性范圍分別為0.01-5 mg·L~(-1)和0.1-50 mg·L~(-1);最低檢出濃度為0.005 mg·L~(-1);提取回收率均大于72%;方法回收率為92.07～102.05%;日內(nèi)及日間變異均小于10%。2、甲基苯丙胺在家兔體內(nèi)的毒代動(dòng)力學(xué)過(guò)程呈一級(jí)動(dòng)力學(xué)特征,符合二室開(kāi)放模型。合用乙醇后不改變其模型類(lèi)型。甲基苯丙胺單用和與乙醇合用的主要毒代動(dòng)力學(xué)參數(shù)分別為Cmax 為1.457±0.094 mg·L~(-1) 與1.648±0.127 mg·L~(-1) 、Tmax 為1.557±0.078h 與1.148±0.034h 、t1/2(ka) 為0.384±0.052h 與0.179±0.028h、Ka 為1.746±0.238 h~(-1) 與3.647±0.519h~(-1) 、α為0.746±0.146h~(-1)與0.913 ±0.138h~(-1)、β為0.234±0.037h~(-1)與0.245±0.036h~(-1)、CL 為1.769±0.114L·h~(-1)·kg~(-1) 與1.674±0.160 L·h~(-1)·kg~(-1) 、V/F 為8.912±0.446 L·kg~(-1) 與9.302±0.646L·kg~(-1)、AUC 為16.188±0.528 mg·h·L~(-1) 與16.919±0.911
[Abstract]:Objective to establish a GC/MS method for qualitative and quantitative analysis of methamphetamine and its main active metabolite amphetamine in biological samples, and to compare the toxicity of methamphetamine with methamphetamine combined with ethanol in rabbits. The dynamic changes of vital signs before and after administration were observed. Methods: 1, GC / MS was used to detect SKF525A in serum and urine samples, and then SKF525A was added to the serum and urine samples. The derivatization of TFAs by ether extraction was determined by GC / MS scanning. The pharmacokinetics of methamphetamine was studied by ion-scanning sim. 2. The methamphetamine group was given methamphetamine at the dose of 15mg (kg ~ (-1), the ethanol group was administered with 3 g 路kg ~ (-1) ethanol, and then the methamphetamine was given 15 mg / kg ~ (-1) of methamphetamine by intragastric administration. The dose of methamphetamine was 15 mg 路kg ~ (-1) and the dose of methamphetamine was 15 mg 路kg ~ (-1) ~ (-1). Blood and urine samples were collected at different time points before and after administration (carotid blood was collected and serum was separated; urinary catheter was collected and urine concentration was measured by GC/MS method. 3P97 program was used to fit the atrioventricular model and calculate the pharmacokinetic parameters. The vital signs were monitored by the physiological function experiment system: BL-5. The main vital signs such as ECG, blood pressure and respiration were recorded in the whole process. Results the linear ranges of methamphetamine and amphetamine in serum and urine were 0.01-5 mg / L ~ (-1) and 0.1-50 mg / L ~ (-1), respectively. The lowest detectable concentration was 0.005 mg 路L ~ (-1) ~ (-1). The recoveries were all greater than 722.05. The pharmacokinetic process of methamphetamine in rabbits showed first-order kinetic characteristics. In accordance with the two-compartment open model. The model type was not changed after ethanol treatment. 鐢插熀鑻笝鑳哄崟鐢ㄥ拰涓庝箼閱囧悎鐢ㄧ殑涓昏姣掍唬鍔ㄥ姏瀛﹀弬鏁板垎鍒負(fù)Cmax 涓，

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