氯胺酮在家兔体内的毒物代谢动力学

目的研究氯胺酮及其代谢物去甲氯胺酮在家兔体内的毒物代谢动力学特征。方法家兔以氯胺酮0.15g/kg剂量灌胃,分别于给药前和给药后不同时间点收集血液和尿液,血清和尿液中氯胺酮及代谢物用GC-MS法定性、GC-NPD法定量检测,WinNorLin软件拟合房室模型并计算毒物代谢动力学参数。全程记录实验动物主要生命体征变化。结果氯胺酮和代谢物去甲氯胺酮在家兔体内的毒物代谢动力学过程均呈一级动力学特征,符合二室开放模型,氯胺酮毒物代谢动力学方程为ρt=121.760e-0.025t+0.980e-0.002t+4.579 e-0.021t,去甲氯胺酮毒物代谢动力学方程为ρt=640.919 e-0.03t+1.023 e-0.001t+9.784 e-0.031t。血液中氯胺酮质量浓度达峰时间为(40.950±12.098)min,血峰质量浓度为(9.015±1.344)μg/mL,消除半衰期为(430.370±28.436)min。给药后30～240 min内氯胺酮在血清和尿液中的质量浓度之间具有动态平衡的中度相关性。家兔给药后30min出现中毒症状,120min后渐恢复正常。结论建立的氯胺酮毒物代谢动力学方程和参数...     

甲基苯丙胺和氯胺酮在家兔体内毒代动力学及相互影响

目的比较家兔单独静脉注射甲基苯丙胺、氯胺酮及二种药物联合静注时的毒物代谢动力学过程,评价二种药物毒代动力学的相互作用。方法单用甲基苯丙胺组以3mg/kg剂量家兔静脉注射甲基苯丙胺,单用氯胺酮组以30mg/kg剂量家兔静脉注射氯胺酮,合用组以相同剂量同时注射两种药物。分别于给药后不同时间点收集血浆标本,测定各时间点药物浓度,WinNonLin软件拟合毒代动力学房室模型并计算参数。结果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,符合单室模型,合用氯胺酮后不改变其模型类型。氯胺酮在家兔体内的毒代动力学过程呈一级动力学特征,符合单室模型,合用甲基苯丙胺后符合二室模型。结论甲基苯丙胺和氯胺酮可以相互延缓其在体内的消除过程,增加彼此在体内的吸收,从而延长作用时间。     

乙醇对氯胺酮在家兔体内毒物代谢动力学的影响研究

目的研究乙醇对氯胺酮在家兔体内毒物代谢动力学行为的影响。方法实验家兔分为单用氯胺酮组、氯胺酮与乙醇合用组及对照组,三组动物分别灌胃氯胺酮0.15 g/kg、乙醇3.0g/kg与氯胺酮0.15 g/kg及等体积生理盐水。分别于给药前和给药后不同时间点收集血、尿标本,GC和GC/MS法测定氯胺酮和代谢物去甲氯胺酮浓度,WinNor-Lin软件拟合房室模型并计算氯胺酮和去甲氯胺酮毒物代谢动力学参数。结果氯胺酮在家兔体内的毒物代谢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房室类型。合用乙醇组家兔体内氯胺酮的K10、AUC和β均大于单用氯胺酮组,而T1/2K10、T1/2β、A和Cmax均小于单用氯胺酮组,两组之间存在显著性差异(P0.05);V/F、K01、K12、K21、T1/2K01、α、T1/2α、Tmax和B等参数两组之间无显著性差异(P0.05)。合用乙醇组家兔体内氯胺酮的代谢物去甲氯胺酮的K01、A、B和Cmax等参数均大于单用氯胺酮组,而T1/2K01、Tmax均小于单用氯胺酮组,两组之间存在显著性差异(P0.05);V/F、K10、K12、K21、AUC、T1/2K10、T1/2α、T1/2β、β等参数两组之间无显著性差异(P0.05)。结论乙醇可加快氯胺酮在体内的消除过程,促进其转化为去甲氯胺酮,对于氯胺酮与乙醇合并滥用的鉴定,应考虑两者的相互作用。     

甲卡西酮及其代谢物在大鼠体内的毒物代谢动力学

目的研究甲卡西酮及其代谢物卡西酮、麻黄碱和伪麻黄碱的毒物代谢动力学特征。方法大鼠分别以甲卡西酮17.25mg/kg和34.5mg/kg经腹腔注射给药,给药后不同时间点经内眦静脉采血,血液中甲卡西酮及其代谢物卡西酮、麻黄碱和伪麻黄碱用HPLC-MS/MS定性、定量检测,DAS3.2.8药代动力学软件拟合动力学方程并计算毒物代谢动力学参数。结果甲卡西酮原体在大鼠血液中的代谢动力学过程符合一级吸收二室开放模型,达峰时间在给予剂量间无明显差异,剂量可以明显导致消除半衰期的延长。低剂量组代谢动力学方程为C=10515.971×e~(-0.024t)-10515.919×e~(-0.144t),高剂量组代谢动力学方程为C=12410.093×e~(-0.015t)-12409.465×e~(-0.169t)。甲卡西酮和卡西酮的检出时限为24h,麻黄碱和伪麻黄碱的检出时限均为2h。甲卡西酮和卡西酮在血液中的浓度比随注射时间的变化不受药物在体内的吸收过程影响,呈指数关系。结论本研究建立的甲卡西酮毒物代谢动力学方程和参数,代谢物的检出时限及与吸毒时间的变化规律可以为甲卡西酮吸毒鉴定的合理取样,原型和代谢物的检出,浓度关系推断吸毒时间以及法医学鉴定提供理论和实验依据。     

甲基苯丙胺滥用与司来吉兰服用的区分:尿液中甲基苯丙胺和苯丙胺的手性分析

目的考察司来吉兰及其代谢物在尿液中的含量变化,并结合实际案例探讨手性分析区分甲基苯丙胺滥用与司来吉兰服用的可行性。方法采用CHIROBIOTICTM V2手性液相色谱柱对尿液样品进行手性分离和液相色谱-串联质谱(LC-MS/MS)法测定,并对司来吉兰服药志愿者尿样、疑服用司来吉兰的涉毒人员尿样进行甲基苯丙胺和苯丙胺的手性分析。结果服用5 mg司来吉兰后,尿液中司来吉兰的检出时限仅为7h。尿液中R(-)-甲基苯丙胺和R(-)-苯丙胺约在7h质量浓度最高,分别为0.86μg/m L和0.18μg/m L,并在80 h和168 h后无法检出。应用该方法成功分析了疑服用司来吉兰的涉毒人员尿液中甲基苯丙胺和苯丙胺的来源。结论甲基苯丙胺和苯丙胺的手性分析以及司来吉兰代谢物检测可区分甲基苯丙胺滥用与司来吉兰服用。     

乌头碱在家兔体内的代谢动力学初步研究

本文应用甲醇-0.05mol/L碳酸铵水溶液-二氯甲烷(90:10:2)作流动相,在YWGC_(18)H_(37)反相键合相色谱柱上分离乌头碱和内标,用紫外分光检测器在235nm外定量,改进了动物组织内痕量乌头碱的HPLC检测法。运用该法检测家兔静脉注射乌头碱后的血毒物浓度,初步研究了乌头碱在家兔体内的代谢动力学过程,表明其体内过程符合开放二室模型,T_(1/2α)=1.4682min,T_(1/2β)=34.1379min。体内乌头碱可以原形由尿和胆汁中排出,但以前6h尿排泄为主。     

GC法检测血液和尿液中甲基苯丙胺和咖啡因

目的建立同时测定血、尿中甲基苯丙胺和咖啡因含量的方法。方法应用GC／NPD技术,以4-苯基丁胺为内标,直接碱化,用氯仿提取,三氟乙酸酐衍生化,8CB熔融石英毛细管柱（30m×0．25mm×0．25μm）分析。结果生物样品中甲基苯丙胺与咖啡因在0．012—7．5μg/mL浓度范围内线性关系良好,检测限（S／N=3）依次为1．2ng／mL,0．6ng／mL（血）;1．6ng／mL,0．8ng／mL（尿）。苯丙胺在0．017—10．0μg／mL浓度范围内线性关系良好,检测限为1．6mg／mL（血）,3．2ng／mL（尿）。所有样本回收率均大于85％。结论本方法准确、灵敏,适用于血、尿中甲基苯丙胺及其代谢物苯丙胺的三氟乙酸酐衍生化物和咖啡因的同时检测,为判定滥用毒品种类、追查毒品来源以及研究生物体内甲基苯丙胺和咖啡因的交互影响提供了检测手段。     

HPLC-MS/MS法检测生物样品中的手性苯丙胺类药物和司来吉兰

目的建立全血、尿液中手性甲基苯丙胺、手性苯丙胺和司来吉兰同时分析检测的方法。方法全血、尿液经Oasis PRiME MCX固相萃取柱前处理,采用Phenomenex Lux AMP(150×3.0mm,3μm)手性液相色谱柱,以甲醇-5mmol/L碳酸氢铵水溶液(p H=11)为流动相,梯度洗脱,流速为0.35m L/min,以正离子多反应监测(MRM)模式检测,扫描时间21min。结果甲基苯丙胺两种对映异构体、苯丙胺两种对映异构体和司来吉兰在1-500ng/m L的范围内线性关系良好(各物质r~2 0.99);甲基苯丙胺两种对映异构体的检出限为0.05ng/m L,定量限为0.1ng/m L,苯丙胺两种对映异构体和司来吉兰的检出限为0.1ng/m L,定量限为0.5ng/m L;在低(5ng/m L)、中(50ng/m L)、高(200ng/m L)三个添加浓度下,各目标物的绝对回收率和基质效应均在可接受的范围内,日内精密度和日间精密度均小于12.61%。应用该方法对口服司来吉兰的比格犬的血液和尿液进行检测,结果表明仅存在司来吉兰原体、代谢物R-甲基苯丙胺和R-苯丙胺。结论本研究建立了全血、尿液中手性甲基苯丙胺、手性苯丙胺和司来吉兰的HPLCMS/MS定性、定量分析检测方法,该方法操作方便,灵敏度高,可为司法实践中法医毒物鉴定提供一定参考。     

阿普唑仑在家兔体内的分布研究

建立生物检材内阿普唑仑的薄层扫描定性定量检测方法，研究阿普唑仑在染毒家兔体内的分布情况。家兔按21mg/Kg剂量灌胃染毒后4h，其体内肝、脾、肾、肺、心、脑、血、胆汁和尿内阿普唑仑的浓度分别为19．6±6．1、3．3±0．5、3．5±0．3、0．4±0．1、0．4±0．1、1．6±1．8、4．0±1．3、20．4±8．5和8.6±2．4（ug／g或ug／ml）。阿普唑仑在染毒家兔体内的分布不均匀，血、胆汁和尿是阿普唑仑中毒死者毒物分析较好的检材。     

氯氰菊酯及其代谢物在犬胆汁中的代谢动力学研究

目的研究氯氰菊酯及其代谢物在犬胆汁中的毒物动力学,为氯氰菊酯中毒的法医学鉴定提供实验依据。方法 6只雄性犬胆囊造瘘术后,经口灌胃1/4LD50剂量的氯氰菊酯,于不同时间点收集胆汁,二氯甲烷液液萃取法提取,高效液相色谱-串联质谱仪分析,MRM记录方式,保留时间和定性离子对定性,内标法和标准曲线法定量检测其中氯氰菊酯(CYM)、3-苯氧基苯甲酸(3-PBA)、二氯菊酸(DCVA)含量,Win Nonlin拟合C-T曲线,计算毒代动力学参数。结果经口灌胃1/4LD50氯氰菊酯后,氯氰菊酯及其代谢物在犬胆汁中的毒物动力学过程均符合一级动力学模型,达峰时间分别为1.52±0.30、1.29±0.04、0.93±0.41 h,达峰浓度分别为0.38±0.03、7.9±1.32、30.9±16.24μg/m L,半衰期分别为3.93±0.71、1.36±0.11、4.49±2.81 h。结论经口灌胃后氯氰菊酯及其代谢物3-苯氧基苯甲酸、二氯菊酸的毒物动力学符合一级吸收代谢动力学模型,模型和参数可以为氯氰菊酯中毒的法医学鉴定提供实验依据。     

甲基苯丙胺在豚鼠毛发中分布及转化的初步研究

目的对甲基苯丙胺在豚鼠毛发中分布及转化机制进行初步研究。方法利用GC/MS,GC/NPD法,测定单次及多次给药豚鼠毛发中MAP、AP的含量变化过程,考察给药剂量与毛发中MAP、AP的含量间的关系,并研究毛发颜色对染毒豚鼠毛发中MAP、AP含量的影响。结果单次及多次给药豚鼠毛发中代谢产物AP均高于原体MAP,给药时间及给药剂量与毛发中MAP、AP的含量显著相关,同体豚鼠黑色毛发中的MAP、AP含量均明显高于棕色、白色毛发。结论给药方式、给药剂量及毛发颜色对豚鼠毛发中MAP、AP的含量均有显著影响。     

Preliminary observations of the effect of methamphetamine in decomposing tissues on the development rate of Parasarcophaga ruficornis (Diptera: Sarcophagidae) and implications of this effect on the estimations of postmortem intervals.

Larvae of Parasarcophaga ruficornis (Fabricius) (Diptera: Sarcophagidae) were reared on tissues from rabbits administered different dosages of methamphetamine to study the effects of this drug on development of this species. The rabbits were given 37.5, 71.4, and 142.9 mg of methamphetamine via ear vein infusion. From Hours 30 to 60, larvae feeding on tissues from rabbits receiving 71.4 and 142.9 mg of methamphetamine developed more rapidly than larvae from the control colony and those feeding on tissues from the rabbit receiving 37.5 mg of methamphetamine. The time required for pupariation was significantly greater for colonies fed on tissues from methamphetamine-dosed rabbits than for the control. These differences were sufficient to alter postmortem interval estimates based on larval development by up to 18 h and estimates based on puparial development by up to 48 h. The presence of methamphetamine or amphetamine could not be detected in Diptera larvae in this experiment using radioimmunoassay techniques, as there was a nonspecific reaction, resulting in a false positive.     

Methamphetamine and amphetamine concentrations in postmortem rabbit tissues

The feasibility of detecting methamphetamine and its major metabolite, amphetamine, in postmortem tissues over a 2-year period was examined. It is important to determine if the abuse and toxic effects of drugs can be proved from evidence found in decayed, submerged, or stained tissue materials. The blood, urine, liver, skeletal muscle, skin and extremity bones from rabbits given methamphetamine intravenously were kept at room temperature, under 4 different conditions: sealed in a test tube, dried in the open air, submerged in tap water and stained on gauze. Methamphetamine was present in all the samples, with slight change in concentration in case of sealed and air dried tissues. Changes varied in bones kept in water. There were considerable decreases in methamphetamine in blood and urine stains. Despite long term storage, drug abuse and/or toxicity could be determined, in all tissues examined.     

A fatal methamphetamine poisoning associated with hyperpyrexia

After self-administration of 0.05g of methamphetamine hydrochloride intravenously on three occasions at intervals of 3h, a 25-year-old female methamphetamine abuser ingested approximately 1.5 g of methamphetamine hydrochloride, and was found dead 3–4 h later. Complete rigor mortis was observed 1–2 h after death and the rectal temperature was 38.4°C 3–4 h after death.Distribution of methamphetamine and amphetamine in the body was analyzed by chemical ionization mass fragmentography. Amphetamine/methamphetamine concentrations (μ mol/100 g) were $\text{0.26}\text{28.8}$ in blood, $\text{0.64}\text{68.2}$ in brain, $\text{0.96}\text{117.1}$ in liver, $\text{0.53}\text{50.6}$ in kidney, and $\text{1.49}\text{1045}$ in stomach contents. Total amount of methamphetamine hydrochloride in stomach contents was 11.6mg.Amphetamine in tissues was a metabolite of methamphetamine, and amphetamine in stomach contents resulted from excretion into saliva and gastric mucous excretion. With rectal temperature at death estimated at more than 41°C, it would seem that hyperpyrexia played an important role in causing death from methamphetamine poisoning.     

CI-mass fragmentographic analysis of methamphetamine and amphetamine in human autopsy tissues after acute methamphetamine poisoning

A 22-year-old male methamphetamine abuser was put under police protection owing to his abnormal state of excitation, but died 1 h later. Distribution of methamphetamine and amphetamine in the body was analyzed by the chemical ionization mass fragmentographic method. Amphetamine/methamphetamine concentrations (μmol/100 g) were $\text{0.24}\text{5.59}$ in blood, $\text{0.41}\text{9.43}$ in liver, $\text{0.41}\text{10.02}$ in brain, $\text{0.37}\text{9.80}$ in kidney, $\text{0.18}\text{4.57}$ in muscle, $\text{0.02}\text{0.63}$ in subcutaneous fat and $\text{1.87}\text{1464}$ in gastric contents. Total amount of methamphetamine hydrochloride in stomach contents was about 54 mg. Amphetamine concentrations in tissues ranged from 3.2% to 4.3% of methamphetamine, and was 0.1% in stomach contents. Amphetamine in tissues seems to be a metabolite of methamphetamine, and amphetamine in gastric contents is presumed to result from gastric mucous excretion. The blood concentration of methamphetamine was at a fatal level, and the total amount of the drug in gastric contents indicates that fatal poisoning occurred by ingestion.     

分子印迹固相萃取法在血中苯丙胺类毒品分析中的应用

目的建立分子印迹固相萃取（MISPE）、GC/MS分析方法,用于血液中苯丙胺类毒品检测。方法 10mmol/L醋酸铵缓冲液（pH8.0）4倍稀释空白添加血液,1mL甲醇,1mL10mmol/L醋酸铵缓冲液（pH8.0）活化苯丙胺类分子印迹固相萃取柱;2×1mL去离子水、1mL60%的乙腈去离子水、1mL1%醋酸乙腈洗涤杂质;2×1mL1%甲酸/甲醇洗脱,洗脱液挥干定容,经GC/NPD、GC/MS分析检测。结果各种苯丙胺类毒品回收率均在90%以上,在20～5 000ng/mL浓度范围内线性关系良好,r2为0.995 7～0.998 9,LOQ在16～30ng/mL之间,LOD在8～15ng/mL之间。结论本方法回收率高,净化效果显著,稳定性好,杂质干扰少,可用于血液中低浓度苯丙胺类毒品的分析检测。     

The use of cyclohexanone as a "derivatizing" reagent for the GC-MS detection of amphetamines and ephedrines in seizures and the urine

A GC-MS method has been developed for the detection of amphetamine, methamphetamine, and the ephedrines, in seizures and the urine, based on on-GC condensation (derivatization) with cyclohexanone. The method is simple: the dried seizure material or the urine extract was mixed with cyclohexanone and injected into the GC-MS. The method was found to be superior to the methods based on acyl and trimethylsilyl (TMS) derivatization. Unlike for the acyl and TMS derivatives, the molecular and fragment ions of the cyclohexanone condensation products (cyclohexanone derivatives) were of substantial abundance, a useful property in unambiguous compound characterization. Furthermore, the high stability of the "derivatizing" reagent, cyclohexanone, compared with acyl and TMS derivatizing reagents, is a useful property in method development. The present method has proved selective and, tentatively, sensitive enough in the following areas (where methods based on acyl and TMS derivatization, as tested in this laboratory, have failed): (a) detection of amphetamine as a metabolite of methamphetamine; (b) detection of norpseudoephedrine as a metabolite of pseudoephedrine; (c) detection of amphetamine as an impurity of methamphetamine; (d) detection of cathine (norephedrine) as a constituent of Khat leaves; and (e) differentiation of Khat use from phenylpropanolamine use.