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。     

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...     

SPE-HPLC/MS/MS法检测人唾液中地西泮及其代谢物

目的采用固相萃取-高效液相色谱-串联质谱法(SPE-HPLC/MS/MS)检测人唾液中地西泮及其代谢物。方法采用固相萃取法(SPE)处理唾液,HPLC/MS/MS法检测,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。结果地西泮及其代谢物去甲地西泮、去甲羟基西泮、去甲羟基地西泮葡萄糖醛酸苷(OG)、羟基地西泮葡萄糖醛酸苷(TG)的检测限在0.01ng/m L~0.5ng/m L之间,线性范围0.1ng/m L或0.5ng/m L~100ng/m L,回收率为84.9%~106%。口服5mg地西泮后15d内唾液中可检出地西泮及去甲西泮,但检出时间有个体差异,但去甲羟基西泮、TG和OG则不能检出。结论 SPE-HPLC/MS/MS检测法可应用于人唾液中地西泮及其代谢物的检测。人口服常量地西泮后唾液中可检出地西泮和去甲西泮,且检测窗口期较宽,但存在个体差异。     

度冷丁滥用者毛发分段分析及其结果评价

以度冷丁滥用者为研究对象,在度冷丁滥用者毛发中检出度冷丁及代谢物去甲度冷丁、N一羟甲基度冷丁和N-乙酰度冷丁。60例度冷丁滥用者头发中度冷丁和去甲度冷丁的含量分别为103±130ng／mg和117±143ng／mg。度冷丁稳定地存在于头发中,检出时限至少为药后20个月,而去甲度冷丁则随着离头发根距离的增加而降低。头发分段分析揭示度冷丁在毛干中的分布和滥用史、剂量和含量存在相关性。     

血中水合氯醛及其代谢物的GC-MS/MS和HPLC-MS/MS检测

目的建立血液中水合氯醛及其代谢物的色谱串联质谱检测方法,用于法医案件的检验。方法血液检材经乙酸乙酯萃取后气质联用选择离子扫描(SIM)检测水合氯醛和三氯乙醇,经乙腈沉淀蛋白后液质联用负离子模式下多反应监测(MRM)检测三氯乙酸。结果水合氯醛及其代谢物的线性范围分别是100ng/mL～15μg/mL、500ng/mL～20μg/mL和500ng/mL～15μg/mL,线性关系良好,R~2均大于0.998,最低检出限分别为15ng/mL、130ng/mL和30ng/mL,最低定量限分别为50ng/mL、500ng/mL和100ng/mL;日内精密度分别在2.26%～7.31%、3.09%～7.23%和2.79%～5.37%;日间精密度分别在4.14%～7.03%、2.18%～4.43%和2.75%～4.96%;提取回收率分别为92.72%～106.30%、94.22%～103.70%和89.05%～104.50%。并对水合氯醛相关案件进行检测,心血中水合氯醛浓度为411.34ng/mL,三氯乙醇浓度为9.49μg/mL,三氯乙酸浓度为8.32μg/mL。结论本文建立的水合氯醛及其代谢物的检测方法准确简单快速,可应用于水合氯醛中毒案件的法医学鉴定。     

2'-氯地西泮及其代谢物的药代动力学特征的LC/MS研究

目的利用液质联用法研究2’-氯地西泮及其代谢物在大鼠体内的药代动力学规律。方法SD大鼠经灌胃给药2’-氯地西泮2.625mg/kg,给药后采集不同时间的血样。蛋白沉淀法处理血浆样品后,进样分析。结果2’-氯地西泮及其代谢物在给药后1h均达到最高血药浓度。2’-氯地西泮在大鼠体内的半衰期约为93h,在给药后144h均能检测到。3种代谢产物地洛西泮、氯甲西泮、劳拉西泮在大鼠血浆的检出时限分别24h、144h、48h。结论2’-氯地西泮在大鼠体内吸收较快,半衰期较长,原体药物和代谢物在大鼠体内的检测窗口均较长。该研究可为临床救治2’-氯地西泮中毒患者以及相关案件的侦破提供一定的实验依据。     

血中安定及其代谢物的酶水解研究

目的考察木瓜蛋白酶水解血中安定及其代谢物蛋白结合物的酶解条件,提高安定的提取率。方法采用正交试验确定酶解的最优条件,检材经蛋白酶水解,固相萃取后,应用LC-MS／MS方法进行检测,运用保留时间和MRM（多离子反应监测）方式来对血中安定及其代谢物进行定性定量分析。结果安定、去甲安定、去甲异安定、羟基安定和去甲羟基安定的最佳酶解条件分别为55℃,2．5h,pH7．0,8000U;50℃,1h,pH7．5,8000U;50℃,1h,pH7．5,8000U;50℃,1．5h,pH7．5,8000U;50℃,1．5h,pH7．5,8000U。结论酶水解后的血液中安定及其代谢物检出量明显增加。     

GC-MS/MS法检测生物样品中硫丹含量

目的建立生物样品中硫丹(α硫丹和β硫丹)的气相色谱-串联质谱(GC-MS/MS)检测方法,观察硫丹在水生动物体内的分布,为相关案件的法医学鉴定提供实验依据。方法血液和肌肉样品采用乙腈沉淀蛋白,GC-MS/MS法检测,多反应监测模式扫描,以保留时间和离子比例定性,外标工作曲线法定量。结果血液样品中α硫丹和β硫丹在0.062 5~10μg/mL范围内线性关系良好,相关系数(r)均大于0.99,检出限分别为1 ng/mL和2 ng/mL,定量限分别为4 ng/mL和8 ng/mL。肌肉样品中α硫丹和β硫丹在0.062 5~10μg/g范围内线性关系良好,相关系数(r)均大于0.98,检出限分别为1 ng/g和4 ng/g,定量限分别为4 ng/g和16 ng/g。血液和肌肉样品中α硫丹和β硫丹的准确度为90.76%~108.91%,日内精密度(RSD)为2.35%~8.71%,日间精密度(RSD)为5.44%~10.29%。中毒案件中,在鱼和螃蟹体内各部位均检出硫丹,且不同部位间含量差异均具有统计学意义。结论本研究建立的硫丹GC-MS/MS检测方法快捷、准确、灵敏,适用于微量生物检材中硫丹的检测。硫丹在鱼和螃蟹体内分布不均匀,为硫丹相关法医学鉴定案件中毒物分析检材的采集和分析提供了依据。     

甲基苯丙胺在家兔体内的毒物代谢动力学研究

目的研究甲基苯丙胺及其代谢物苯丙胺在家兔体内的毒物代谢动力学行为。方法GC/MS法测定家兔灌胃甲基苯丙胺后不同时间点血、尿中甲基苯丙胺和代谢物苯丙胺浓度,采用3P97程序进行房室模型拟合以及毒物代谢动力学参数计算。结果甲基苯丙胺和苯丙胺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。甲基苯丙胺在家兔体内Cm ax为1.457 mg/L±0.094 mg/L,Tm ax为1.557h±0.078h,t1/2 ka、t1/2α和t1/2β分别为0.384h±0.052h、1.614h±0.036h和3.007h±0.430h,CL为1.769 L/h/kg±0.114 L/h/kg。甲基苯丙胺的毒物代谢动力学方程为:C t=2.767 e-0.746 t+1.454 e-0.234 t+4.119 e-1.746 t。结论甲基苯丙胺在家兔体内吸收、消除和代谢都较快。建立的甲基苯丙胺毒物代谢动力学方程和参数可为甲基苯丙胺分析的合理取样、从血药浓度推断服毒时间以及甲基苯丙胺滥用的法医学鉴定提供理论依据。     

固相微萃取-气相色谱质谱法测定血浆中的氯氮平浓度

目的建立固相微萃取-气相色谱质谱法测定人血浆中氯氮平浓度的方法。方法以固相微萃取法提取血浆中的氯氮平,萃取头为100μm聚二甲基硅氧烷,洛沙平作内标,用气相色谱质谱选择离子法进行检测。结果本文建立的方法在5~2000 ng/ml浓度范围内呈线性关系,检测限为0.1 ng/ml(信噪比>3),低、中、高浓度(100、500、1000 ng/ml)平均相对回收率分别为98.6%、94.6%和94.6%,日内、日间RSD分别小于7.4%和7.1%。结论本文建立的固相微萃取-气相色谱质谱法灵敏度高、准确度好、操作简便,适用于氯氮平急性中毒案件的检测。     

GC—MS同时测定血液中苯海索、氯丙嗪和氯氮平

目的建立GC—MS同时测定血液中苯海索、氯丙嗪和氯氮平的方法。方法血液中加入内标SKFszs。．在pH〉10条件下用V（苯）：v（乙酸乙酯）=1：l提取,用GC—MS全扫描法进行定性检测：以地西泮一d;为内标,样品在pH〉10条件下用V（苯）：v（乙酸乙酯）=l：1提取,用GC—MS选择离子监测方法进行定量检测．结果苯海索、氯丙嗪和氯氮平在20～10000ng／mL范围内呈线性关系,最小检测限分别为0．3、0．3和0．7n幽L（信噪比≥3）,方法回收率为79．9％～85．5％,日内、日间精密度均小于5．1％。结论本方法可同时分析血液中苯海索、氯丙嗪和氯氮平,方法灵敏度高、快速、操作简便,适用于苯海索、氯丙嗪和氯氮平的血药浓度监测和急性中喜案件竹枪测     

Detection and disposition of JWH-018 and JWH-073 in mice after exposure to "Magic Gold" smoke

The disposition in mice of the cannabimimetics JWH-018 and JWH-073 in blood and brain following inhalation of the smoke from the herbal incense product (HIP) "Magic Gold" containing 3.6% JWH-018, 5.7% JWH-073 and less than 0.1% JWH-398 (w/w) is presented. Specimens were analyzed by HPLC/MS/MS. The validation of the method is also presented. Five C57BL6 mice were sacrificed 20 min after exposure to the smoke of 200 mg of "Magic Gold" and a second set of five exposed mice were sacrificed after 20 h. Twenty minutes after exposure to "Magic Gold" smoke, blood concentrations of JWH-018 ranged from 42 to 160 ng/mL (mean: 88 ng/mL ± 42) and those of JWH-073 ranged from 67 to 244 ng/mL (mean: 134 ng/mL ± 62). Brain concentrations 20 min after exposure to "Magic Gold" smoke for JWH-018 ranged from 225 to 453 ng/g (mean: 317 ng/g ± 81) and those of JWH-073 ranged from 412 to 873 ng/g (mean: 584 ng/g ± 163). Twenty hours after exposure to "Magic Gold" smoke, JWH-018 was detected and quantified in only two of the five blood samples. Blood concentrations of JWH-018 were 3.4 ng/mL and 9.4 ng/mL. JWH-073 was detected in only one blood specimen 20 h after exposure at 4.3 ng/mL. Brain concentrations 20 h post exposure for JWH-018 ranged from 7 to 32 ng/g (mean: 19 ng/g ± 9). JWH-073 was not detected in 20 h post exposure brain specimens. JWH-398 was not detected in any of the blood or brain samples. The disposition data presented with the limited data available from human experience provide reasonable expectations for forensic toxicologists in JWH-018 or JWH-073 cases. As with THC after smoking marijuana, blood and brain concentrations of JWH-018 and JWH-073 after HIP smoking can be expected to rise initially to readily detected values, and then drop dramatically over the next few hours to several ng/mL or ng/g, and finally to be at extremely low or undetectable concentrations by 24h apparently due to extensive biotransformation, and redistribution to body fat.     

Case report: Etizolam and its major metabolites in two unnatural death cases

A simultaneous analytical method for etizolam and its main metabolites (alpha-hydroxyetizolam and 8-hydroxyetizolam) in whole blood was developed using solid-phase extraction, TMS derivatization and ion trap gas chromatography tandem mass spectrometry (GC-MS/MS). Separation of etizolam, TMS derivatives of alpha-hydroxyetizolam and 8-hydroxyetizolam and fludiazepam as internal standard was performed within about 17 min. The inter-day precision evaluated at the concentration of 50 ng/mL etizolam, alpha-hydroxyetizolam and 8-hydroxyetizolam was evaluated 8.6, 6.4 and 8.0% respectively. Linearity occurred over the range in 5-50 ng/mL. This method is satisfactory for clinical and forensic purposes. This method was applied to two unnatural death cases suspected to involve etizolam. Etizolam and its two metabolites were detected in these cases.     

Forensic appraisal of death due to acute alcohol poisoning: three case reports and a literature review

Death due to acute alcohol poisoning lacks specific anatomical characteristics, compared with other deaths due to drug poisoning. We report three forensic cases of death from acute alcohol poisoning due to inhibition of the respiratory centre and eventual asphyxia. Blood alcohol concentrations in the three fatalities were 5.28, 3.33 and 3.78 mg/mL, respectively. Lethal doses and blood alcohol concentrations showed differences between individuals. Detailed auxiliary tests besides autopsy were undertaken. These cases show that forensic scientists should exclude other causes of death, combine the autopsy with auxiliary tests, and then make an appraisal.     

高效液相色谱法测定人血液、尿液中的2,4-D丁酯

目的建立检测血液、尿液中2,4-D丁酯的高效液相色谱分析方法。方法采用正己烷为样品萃取溶剂,色谱柱为Zorbax SB-Aq柱,流动相为V（甲醇）∶V（水）=60∶40。结果 2,4-D丁酯在血液和尿液中的线性范围分别为0.10～10.00μg/mL（r≥0.999 8）和0.08～8.00μg/mL（r≥0.999 5）,检测限分别为0.002 0μg/mL和0.001 8μg/mL,准确度为94.5%～104.5%,日内、日间精密度≤4.5%。结论本研究建立的血液、尿液中2,4-D丁酯的提取和HPLC检测方法,可应用于2,4-D丁酯中毒的快速检验和中毒死亡的法医学鉴定。     

氯氮平在家兔体内死后再分布规律研究

目的阐明死后48h内家兔体内氯氮平再分布规律,为相关法医鉴定工作提供借鉴。方法取家兔15只,随机分为5组,以氯氮平灌胃,分别于死后0、6、12、24、48h取心血、外周静脉血、尿液、肝组织检测氯氮平浓度。结果家兔死亡后心血、外周静脉血、肝脏氯氮平浓度不断升高,尿液氯氮平浓度不断降低;死后早期浓度变化率大于晚期浓度变化率。死后48h心血、外周静脉血、肝脏、尿液氯氮平浓度分别为死后0h各检材氯氮平浓度的418%、193%、154%和29%。结论死亡一段时间后,提取生物检材,检测出的氯氮平浓度并不能准确反映刚死时的实际浓度。     

超分子溶剂萃取-气相色谱-串联质谱法检测尿液中苯二氮䓬类药物

目的建立一种尿液中9种苯二氮?类药物的超分子溶剂样品气相色谱-串联质谱(gas chromatography-tandem mass spectrometry,GC-MS/MS)分析方法。方法含9种苯二氮?类药物对照品的尿液样品用四氢呋喃和1-己醇组成的超分子溶剂进行液液萃取,取溶剂层氮吹至干,残余物用甲醇复溶后进行GC-MS/MS分析,数据采集方式为多反应监测模式,采用内标法定量。结果尿液中地西泮、咪达唑仑、氟硝西泮和氯氮平质量浓度在1~100ng/mL,劳拉西泮和阿普唑仑质量浓度在5~100ng/mL,硝西泮和氯硝西泮质量浓度在2~100ng/mL,艾司唑仑在质量浓度0.2~100ng/mL范围内具有良好的线性关系,相关系数为0.9991~0.9999,定量下限为0.2~5ng/mL,提取回收率为81.12%~99.52%,日内精密度[相对标准偏差(relative standard deviation,RSD)]和准确度(偏倚)分别小于9.86%、9.51%;日间精密度(RSD)和准确度(偏倚)分别小于8.74%、9.98%。室温和-20℃条件下,尿液中9种药物在15d内具有良好的稳定性。8名志愿者单摄口服阿普唑仑片后,在8~72h内尿液中阿普唑仑的质量浓度为6.54~88.28ng/mL。结论本研究建立的尿液中9种苯二氮?类药物的超分子溶剂萃取-GC-MS/MS分析方法,简便、快速、准确、灵敏,可为临床治疗及司法鉴定中苯二氮?类药物中毒监测提供技术支持。     

Suspected clozapine poisoning in the UK/Eire, 1992-2003

OBJECTIVE: Toxicological analyses are often performed to investigate suspected poisoning, but the interpretation of results may not be straightforward. We studied suspected poisoning cases 1992-2003 where blood clozapine and N-desmethylclozapine (norclozapine) were measured in order to assess the relationship of these parameters to outcome. METHODS: Samples were referred from clinicians, pathologists/coroners, or via the Clozaril Patient Monitoring Service (CPMS, Novartis). Information was gathered from clinical, post-mortem, or coroners' reports. RESULTS: There were seven fatal [five male, two female; median (range) age 28 (24-41) year] and five non-fatal [four male, one female; median age 35 (26-41) year] clozapine overdoses. The median post-mortem blood clozapine and norclozapine concentrations were 8.2 (3.7-12) and 1.9 (1.4-2.4)mg/L, respectively [median clozapine:norclozapine ratio 4.4 (2.9-5.1)]. The median plasma clozapine and norclozapine concentrations (first or only sample) were 3.9 (1.7-7.0) and 0.40 (0.30-0.70)mg/L, respectively [median clozapine:norclozapine ratio 7.6 (5.3-18)] in the remainder. These overdoses were in patients who were poorly or non-adherent to clozapine, or who had taken tablets prescribed for someone else. In 54 further people who died whilst receiving clozapine [38 male, 16 female; median age 41 (22-70) year], the median post-mortem blood clozapine and norclozapine concentrations were 1.9 (0-7.7, n = 43) and 1.4 (0-6.0, n = 39)mg/L, respectively [median clozapine:norclozapine ratio 1.5 (0.4-7.6, n = 38)]. The median post-mortem increase in blood clozapine and norclozapine as compared to the most recent ante-mortem measurement was 489 (98-5,350)% and 371 (139-831)%, respectively [median sample time before death 14 (0-30, n = 21) days]. CONCLUSION: Clozapine poisoning cannot be diagnosed on the basis of blood clozapine and norclozapine concentrations alone. The analysis of ante-mortem blood specimens collected originally for white cell count monitoring and the blood clozapine:norclozapine ratio may provide additional interpretative information.