甲基苯丙胺在家兔体内的毒代动力学以及乙醇对其毒代动力学的影响

发布时间：2018-05-27 20:05

  本文选题：甲基苯丙胺 + 乙醇　； 参考：《山西医科大学》2005年硕士论文

【摘要】：目的:1、建立生物样品中甲基苯丙胺及其主要活性代谢产物苯丙胺的GC/MS 定性定量分析方法。2、比较研究单用甲基苯丙胺与合用乙醇后的甲基苯丙胺在家兔体内的毒代动力学过程。3、观察实验动物给药前和给药后生命体征的动态变化规律。 方法:1、气相色谱/质谱联用(GC/MS)检测方法:血清、尿液样品中加入内标物SKF525A后碱化,乙醚萃取,TFA 衍生化,GC/MS 全扫描定性,选择离子扫描(SIM)定量分析。2、毒代动力学研究:单用甲基苯丙胺组以15mg·kg~(-1)剂量灌服甲基苯丙胺,合用乙醇组先以3g·kg~(-1)乙醇灌胃,再灌服甲基苯丙胺(15 mg·kg~(-1))。分别于给药前和给药后不同时间点收集血尿标本(颈动脉采血,分离血清;导尿管收集尿液),用GC/MS 方法测定各时间点药物浓度。采用3P97 程序进行房室模型拟合以及毒代动力学参数计算。3、生命体征监测:BL-5 生理机能实验系统全程记录实验动物的心电、血压和呼吸等主要生命体征变化。 结果:1、GC/MS 法检测血清和尿液中甲基苯丙胺与苯丙胺的线性范围分别为0.01-5 mg·L~(-1)和0.1-50 mg·L~(-1);最低检出浓度为0.005 mg·L~(-1);提取回收率均大于72%;方法回收率为92.07～102.05%;日内及日间变异均小于10%。2、甲基苯丙胺在家兔体内的毒代动力学过程呈一级动力学特征,符合二室开放模型。合用乙醇后不改变其模型类型。甲基苯丙胺单用和与乙醇合用的主要毒代动力学参数分别为Cmax 为1.457±0.094 mg·L~(-1) 与1.648±0.127 mg·L~(-1) 、Tmax 为1.557±0.078h 与1.148±0.034h 、t1/2(ka) 为0.384±0.052h 与0.179±0.028h、Ka 为1.746±0.238 h~(-1) 与3.647±0.519h~(-1) 、α为0.746±0.146h~(-1)与0.913 ±0.138h~(-1)、β为0.234±0.037h~(-1)与0.245±0.036h~(-1)、CL 为1.769±0.114L·h~(-1)·kg~(-1) 与1.674±0.160 L·h~(-1)·kg~(-1) 、V/F 为8.912±0.446 L·kg~(-1) 与9.302±0.646L·kg~(-1)、AUC 为16.188±0.528 mg·h·L~(-1) 与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�涓欒兒鍗曠敤鍜屼笌涔欓唶鍚堢敤鐨勪富瑕佹瘨浠ｅ姩鍔涘�﹀弬鏁板垎鍒�涓篊max 涓，

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