Blood concentrations of tetracaine and its metabolite following spinal anesthesia

Blood concentrations of tetracaine and its metabolite, p-butylaminobenzoic acid, were measured after spinal anesthesia with tetracaine which had been administered to patients under going orthopedic surgery. Tetracaine, an ester anesthetic, was given to 10 patients, the dose was 8-14mg, and blood samples were collected 1, 2 and 6h after the injection of tetracaine. We used gas chromatography/mass spectrometry for purposes of analysis. Tetracaine was not detected in any blood sample, but the metabolite was detected in each sample with the mean concentrations of 126.5, 97.9 and 43.3ng/ml at 1, 2 and 6h, respectively. This data will be useful in determination of the cause of death after spinal anesthesia with tetracaine.     

度冷丁在家兔体内的代谢分布研究

建立生物检材中度冷丁及其代谢物去甲度冷丁的GC／NPD系统分析方法,研究染毒家兔体内度冷丁的原体及代谢物分布情况,测定1例肌肉注射度冷丁过量致死者体内度冷丁和去甲度冷丁浓度。组织检材经酸水解后,在碱性条件下用乙醚提取,残余物用25μl甲醇溶解后进行气相分析。度冷丁的提取回收率高于60％,相对标准偏差小于12％;染毒家兔体内度冷丁浓度下降很快,去甲度冷丁浓度较低;度冷丁和去甲度冷丁在染毒家兔各脏器中含量分布除血液外与度冷丁过量致死者体内分布一致,尿中度冷丁和去甲度冷丁浓度最高,肝脏中浓度明显低于其它脏器。此结果为中毒检案的最佳检材选择和对毒物分析结果评价提供了科学依据。     

Distribution of lidocaine and disopyramide in human blood and tissue, a case report of death caused by spinal anesthesia

An 11-year-old girl was anesthetized with hyper-baric solution of lidocaine as spinal anesthesia for an appendectomy in a surgical clinic. Respiratory arrest which occurred soon after the injection, was not discovered for a period of time. Since spontaneous respiration recovered within 2 h of intensive resuscitation, the patient was transferred to a community hospital for intensive care. Ten hours after the spinal anesthesia, she died of cardiac failure. The concentration of lidocaine in the brain was 5-10 times more than that in other tissues. The relationship between the possibility of malpractice of spinal anesthesia and tissue distribution of the drug was discussed. In addition to lidocaine, a toxic amount of disopyramide, an antiarrhythmic drug, was detected in the body. The distribution of disopyramide was also estimated, and the pharmacokinetics of disopyramide in plasma and tissues were studied experimentally in rats.     

毛发中海洛因及其代谢物的分析综述

对毛发中海洛因及其代谢物—6-单乙酰吗啡和吗啡的提取和检测分析进行了综述。其分析方法大致为6步:收集毛发,清洗毛发,分段,剪(磨)碎毛发,水解,提取净化,检测分析。     

GC／MS法检验血液中双甲脒及其代谢产物

目的建立血液中双甲脒及其代谢产物单甲脒的气质联用定量检测方法。方法采用液-液萃取前处理,考察了不同的提取溶剂和pH值对检测结果的影响,优化了萃取条件。结果在最优条件下,该方法对双甲脒和单甲脒的检出限分别为2ng/mL和3ng／mL,两种目标物在20～2000ng／mL范围内线性关系良好（砰分别为0．9997和0．9992）,血液中双甲脒和单甲脒的回收率为8l％～90％。结论该方法具有良好的灵敏度、重现性、稳定性和专属性,可用于法庭科学与临床学的毒物分析。     

毛发中甲基苯丙胺及代谢产物苯丙胺的分析研究

介绍了毛发中甲基苯丙胺（ MAMP）及代谢产物苯丙胺（ AMP）的 GC/NPD、 GC/MS的定性定量分析方法。毛发用 0.1 mol/L HCl水解, 4－苯基丁胺（ 4－ PBA）为内标,液－液提取,三氟乙酸酐（ TFA）衍生化。毛发用量为 10mg,检出限为 GC/NPD 0.5ng/mg, GC/MS 0.1ng/mg,回收率大于 78％。该方法成功应用于染毒豚鼠毛发中 MAMP及其代谢产物 AMP浓度变化过程的测定。     

利多卡因在蛛网膜下腔麻醉致死犬体内的分布

目的 观察利多卡因蛛网膜下腔致死犬体内的分布及脊髓液、脊髓与血液中利多卡因含量的比值。方法薄层扫描法检测血、脊髓液、侧脑室液、各节段脊髓和各脏器组织中利多卡因含量。结果 蛛网膜下腔麻醉致死犬脊髓液、各节段脊髓、脑、血液和其它各脏器中利多卡因含量分别为485.6±51.5μg/ml、226.8±35.2-353.8±44.0μg/g、44.9±11.51μg/g、40.3±6.5μg/ml和13.5±13.7-38.0±9.8μg/g。脊髓液与血液中利多卡因含量之比为12.4±2.7,各节段脊髓与血液之比为5.7±0.9-9.0±2.6。结论 蛛网膜下腔麻醉致死犬脊髓液中利多卡因含量最高,脊髓中次之,血液和其它组织中含量较低。脊髓液/血液、脊髓/血液比值平均可达12.4和5.7-9.0。     

甲基苯丙胺及其代谢产物在急性中毒豚鼠体内的分布

目的研究甲基苯丙胺 (MAP)及其代谢产物苯丙胺 (AP)在急性中毒豚鼠体内的含量分布。方法应用GC/NPD技术 ,以 4 苯基丁胺 (4 PBA)为内标 ,样品经水解后碱化或直接碱化至pH >11,环已烷混旋提取 ,三氟乙酸酐 (TFA)微波衍生化 ,测定MAP急性中毒豚鼠体液和组织中MAP及AP的含量。结果急性中毒死亡豚鼠体内各器官和体液中MAP及AP含量最高为肺 ;其次为肝、脑、肾、脾、肠、心、血 ;再次为胃、胆汁 ;最少是尿。结论MAP在动物体内代谢迅速 ,组织或体液中MAP和AP浓度的比值与豚鼠给药后存活时间有关     

Extraction of nitrobenzene and its metabolite 3-aminohydroxybenzene from water solutions

The article presents the results of nitrobenzene and 3-aminohydroxibensene extraction from aqueous solutions by means of five organic solvents. The following factors influence on the extraction degree is shown: the nature of the extracting agent, aqueous phase pH, saturation of some extracting agents with water. The number of extractions for isolation of the necessary quantities of the compounds studied is calculated.     

Identification of adrafinil and its main metabolite modafinil in human hair. Self-administration study and interpretation of an authentic case

For several years, the misuse of stimulant substances is increasingly observed both in the field of sport, to improve the functions of the body and therefore to be more performant, and also by non-athletes to make life more tolerable on a daily basis. Adrafinil, 2-((diphenylmethyl)sulfinyl)-N-hydroxyacetamide, is a drug designed for the treatment of narcolepsy by promoting an awakened state, and to treat alertness and neurological symptoms in the elderly. It is primarily metabolized in vivo to an active form, i.e. modafinil, 2-((diphenylmethyl)sulfinyl)acetamide. The World Anti-Doping Agency (WADA) banned these two drugs in sports in 2004. The authors report an authentic case involving adrafinil and modafinil. The laboratory was requested to test for adrafinil in a hair strand collected from a woman found in possession of vials of adrafinil and suspected of trafficking. A specific method was developed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Unlike modafinil (varying from 6.8 to 13.9 ng/mg), adrafinil was not identified in the strand. The interpretation of the results was difficult because this is the first case describing human hair analysis. In order to be able to interpret the results, a self-administration study was conducted after an oral administration to a volunteer (200 mg) whose beard hair was collected 10 days after administration. The analysis of this specimen highlighted the presence of adrafinil at 0.8 ng/mg and modafinil at 0.5 ng/mg. These results demonstrate the dual identification of both compounds after a single consumption, even after administration of a low dose. According to these results, the analysis of the hair strand from the authentic case does not match with a consumption of adrafinil, in accordance with abuse of modafinil alone. Intelligence considered that this was a trafficking case of adrafinil, with no self-consumption.     

血,尿中甲基苯丙胺以及代谢产物苯丙胺的分析研究

介绍了血、尿中甲基苯丙胺及其代谢产物苯丙胺的GC/MS，GC/FID和GC/NPD的定性定量分析方法．样品以4-苯基丁胺为内标，用200μl环己烷直接提取进样或提出物经微波照射快速衍生化后分析．方法简便、快速，回收率高于80％．检出限为2～5ng/ml．建立了体内甲基苯丙胶和苯丙胺的d/l光学对映体测定方法，可用于判断毒品来源及毒作用．     

Tissue concentrations of MDMA and its metabolite MDA in three fatal cases of overdose

The recreational use of amphetamine derivatives has become increasingly popular in our country in past recent years. Their use is especially common among young people participating in dance parties known as "raves." As a direct consequence of their increased use, the number of fatal cases in which these compounds have been involved have increased dramatically since the second half of the last decade. In our laboratory, we have registered 25 cases related to amphetamine derivatives use since 1996. Three of them were deeply studied and the results obtained are presented in this paper. This information may be useful for the interpretation of the results obtained in toxicological analysis in the cases in which death may be attributed to MDMA use.     

HPLC-MS/MS法检测大鼠体内氟胺酮及其代谢物动态分布规律

目的研究氟胺酮及其代谢物(去甲氟胺酮)在大鼠体内动态分布规律,为涉氟胺酮死亡案件法医学鉴定提供实验依据。方法将104只SD大鼠随机分为13组,1组作为空白对照组,其余12组,禁食12h,经腹腔注射0.09mg/kg氟胺酮后,分别在不同时间点(15min、30min、45min、60min、90min、120min、180min、240min、300min、360min、420min、480min)处死,立即取心血、心、肝、脾、肺、肾、脑,用高效液相色谱-三重四级杆质谱HPLC-MS/MS检测各组织中氟胺酮及代谢物去甲氟胺酮的浓度。结果氟胺酮经腹腔注射进入体内后,迅速分布于各组织,且在15min内达最高浓度。在480min内,氟胺酮和去甲氟胺酮在血液中均有分布,且含量均高于其他组织;其他组织中氟胺酮在肝、肾、脾中分布较多;去甲氟胺酮在肝、肾中分布较多。结论氟胺酮及去甲氟胺酮大鼠体内的动态分布规律可以为涉氟胺酮死亡案件提供数据支撑。     

Validity testing of commercial urine cocaine metabolite assays: IV. Evaluation of the EMIT d.a.u. cocaine metabolite assay in a quantitative mode for detection of cocaine metabolite

The EMIT d.a.u. cocaine metabolite assay (EMIT dau) was evaluated in a quantitative mode for analysis of clinical specimens obtained after controlled cocaine administration to human subjects. The quantitative results showed high concordance with those of gas chromatography/mass spectrometry (GC/MS) assays of the same specimens for benzoylecgonine, and no false positive or false negative results were obtained. The evaluation also included analysis of standardized solutions containing benzoylecgonine, cocaine, and other cocaine metabolites and isomers. The EMIT dau antibody demonstrated high selectivity for benzoylecgonine. The precision was somewhat less than that reported earlier for other commercial cocaine metabolite immunoassays. Quantitation of initial screening results from EMIT dau testing can serve as a useful guide for confirmation by GC/MS in forensic science urine testing.     

LC-MS／MS测定尿液中可卡因及其代谢物苯甲酰爱康宁

目的建立尿液中可卡因(cocaine,COC)及其代谢物苯甲酰爱康宁(benzoylecgonine,BZE)的液相色谱-串联质谱分析方法。方法尿液经固相萃取后,用AllurePFP丙基柱分离,以V(甲醇):V(20mmol/L乙酸胺和0.1%甲酸的缓冲溶液)=80∶20为流动相,采用二级质谱多反应监测模式检测COC和BZE。按10mg/kg的剂量对豚鼠腹腔注射可卡因,给药后收集7d尿液。结果尿液中COC和BZE在2.0～100ng/mL质量浓度范围内线性关系良好(r=0.9995),最低检测限(LOD)为0.5ng/mL;回收率大于90%;日内和日间精密度均小于6%;豚鼠尿液中主要检测目标物是BZE,且BZE检测时限也较COC长。结论所建方法灵敏度高,选择性好,适用于尿液中可卡因和苯甲酰爱康宁的检测。     

Determination of 2.4-dinitrophenol,its basic metabolite and 4-oxide diphenyl in biological materials

A possibility was considered to isolate, by using dimethylformamide, 2.4-dinitrophenol, 2-amino-4-nitrophenol and 4-oxid-diphenyl from a biological-origin object. A method of extraction with subsequent chromatography in thin silicon-gel layer was used to purify the isolates from biological materials. The designed technique provides for identifying and for quantitatively defining the discussed phenol structures contained in the isolates from the liver tissue of corpses and human blood.     

Concentrations of cocaine and its major metabolite benzoylecgonine in blood samples from apprehended drivers in Sweden

Cocaine and its major metabolite benzoylecgonine (BZE) were determined in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID) over a 5-year period (2000-2004). Venous blood or urine if available, was subjected to a broad toxicological screening analysis for cannabis, cocaine metabolite, amphetamines, opiates and the major benzodiazepines. Verification and quantitative analysis of cocaine and BZE in blood was done by gas chromatography-mass spectrometry (GC-MS) at limits of quantitation (LOQ) of 0.02mg/L for both substances. Over the study period 26,567 blood samples were analyzed and cocaine and/or BZE were verified in 795 cases (3%). The motorists using cocaine were predominantly men (>96%) with an average age of 28.3+/-7.1 years (+/-standard deviation, S.D.). The concentration of cocaine was below LOQ in 574 cases although BZE was determined at mean, median and highest concentrations of 0.19mg/L, 0.12mg/L and 1.3mg/L, respectively. In 221 cases, cocaine and BZE were together in the blood samples at mean and (median) concentrations of 0.076mg/L (0.05mg/L) and 0.859mg/L (0.70mg/L), respectively. The concentrations of BZE were always higher than the parent drug; mean BZE/cocaine ratio 14.2 (median 10.9) range 1-55. Cocaine and BZE were the only psychoactive substances reported in N=61 cases at mean (median) and highest concentrations of 0.095 (0.07) and 0.5mg/L for cocaine and 1.01 (0.70) and 3.1mg/L for BZE. Typical signs of drug influence noted by the arresting police officers included bloodshot and glossy eyes, agitation, difficulty in sitting still and incoherent speech.     

琥珀胆碱及其代谢物琥珀单胆碱的检验

目的建立液质联用分析琥珀胆碱和琥珀单胆碱的检验方法。方法通过动物实验,采集死前血液与死后心脏血;通过优化色谱-质谱分析条件以及进样顺序,实现了空白干扰物与代谢物的有效分离。结果首次检验了中毒死亡检材中的琥珀单胆碱,并分析琥珀胆碱与琥珀单胆碱的丰度比例以及通过实际案例推断体内琥珀单胆碱的来源。结论提出了必须将琥珀单胆碱列入琥珀胆碱中毒案件的毒物检验目标,可以大大提高生物检材阳性检出率。     

钾中毒死亡家兔的尸体化学变化

目的研究家兔钾中毒死亡后的尸体化学变化特征,为钾中毒的法医学鉴定提供参考。方法采用浓度为0.3%和1%的KCl葡萄糖溶液分别以全速和100滴/min的速度输给家兔,至其死亡,测定家兔输液前后血、尿电解质浓度,比较两种不同输液方式所致钾中毒死亡后尸体化学变化特征。结果输钾前后,家兔血清K (SK)浓度升高,血清Na 、Ca2 、Cl-及HCO3-浓度均降低,全血K (TK)及血清Mg2 浓度变化无显著性差异。0.3%KCl组致死输液时间长于1%组(P=0.006),致死输钾量无显著性差异(P=0.062);TK、血清Na 、Mg2 及Cl-浓度变化值具有显著差异,SK、Ca2 、HCO3-浓度变化值无显著差异;尿量和尿液各电解质浓度指标未见显著性差异。结论尸体SK、TK及血清Mg2 浓度升高,有助于钾中毒的法医学死后诊断。