氯胺酮滥用的毛发分析研究

目的建立毛发中氯胺酮及其代谢物的分析方法并探索氯胺酮进入毛发的机理。方法通过建立豚鼠连续给药(不同剂量)实验模型获取阳性头发和采集氯胺酮滥用者头发,经处理后用GC/MSscan和SIM法分析,以鉴别、确认毛发中氯胺酮及其代谢物。结果豚鼠毛发中氯胺酮的质量分数与给药剂量存在明显的正相关性。毛发中氯胺酮质量分数依白色、棕色、黑色毛发顺序随毛发中黑色素的质量分数增加而增加。豚鼠毛发中氯胺酮与代谢物NK质量分数之比为2.33～12.94,仅在高剂量组的豚鼠毛发中才检测到DHNK,其质量分数与NK接近。15名氯胺酮滥用者黑色头发中均检出原体和代谢物NK,但DHNK少见。豚鼠毛发中代谢物相对质量分数明显高于人。结论本实验结果很好地反映了药物进入毛发代谢过程与药物和黑色素亲和力以及药物的亲脂性密切相关这一规律,但人和动物在药物代谢及进入毛发的难易程度上存在差异。本方法可以用于法庭毒物分析领域头发中氯胺酮的检测。     

胶束液相色谱法在体内毒物分析中的应用

胶束液相色谱法是采用高于临界胶束浓度的表面活性剂溶液作为流动相的反相液相色谱方法。本文概述了胶束液相色谱法的基本原理和在理化分析方面的优势,介绍了其在毒品、巴比妥类镇静催眠药、苯二氮卓艹类催眠镇定药检验等方面的实际应用,认为胶束液相色谱法具有选择性高、适用范围广、生物样品处理简便等优点,可成为毒物分析的一种方法。     

头发中氯硝西泮的分段分析在药物辅助犯罪案件中的作用

目的通过分段分析头发中的氯硝西泮,对药物辅助犯罪案件中受害人的摄药频度及摄药史进行推断。方法采用液氮冷冻研磨技术联合超声浴技术,以液相色谱-串联质谱法,对6名不同案件中受害人的头发分段分析,并测定各头发段中的氯硝西泮及7-氨基氯硝西泮的含量。结果 6名受害人的部分头发段中均检出氯硝西泮及其代谢物7-氨基氯硝西泮,且头发中药物峰值浓度的出现时间与受害人自述摄药时间相一致。结论头发分段分析可提供摄药频度与摄药时间信息,在药物辅助犯罪案件中具有独特的证据价值。     

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。     

催眠抢劫案件中三唑仑药物的检验

三唑仑药是一种新的催眠镇静药。无嗅,浅蓝色片,分子式:C_(17)H_(12)Cl_2N_4结构式: 近两年来,用三唑仑药进行催眠抢劫的案件时有发生。本文采用薄层色谱法、薄层扫描仪对三唑仑药物进行定性分析探论,方法简便,准确、可靠,实用性广。     

氟硝西泮滥用及检测研究进展

具有镇静催眠作用的氟硝西泮曾在世界范围内被滥用,常被用于自杀、谋杀、迷奸、迷抢等案(事)件。近年其又成为俱乐部滥用药物之一。该药物在体内主要经肝脏代谢为7-氨基氟硝西泮和N-去甲基氟硝西泮,且7-氨基氟硝西泮的血药浓度常常大于血液中的母体药物浓度,大约90%的代谢产物经尿液排出,10%经粪便排出。目前报道的相关分析方法主要是对于血液、尿液、毛发、酒水饮品等检材经LLE、SPE、LPME等净化萃取后,采用毛细管电泳法、色谱法、质谱法及各种技术的联用,检测母体药物及相关代谢产物。本文对氟硝西泮的滥用、体内代谢以及样品的提取净化、仪器分析等进行总结,为相关案(事)件的办理提供参考。     

ASE-GC/MS法检测血液中的常见镇静安眠类药物

目的建立ASE-GC/MS技术检测血液中常见镇静安眠类药物的方法。方法采用快速溶剂萃取(ASE)技术,对巴比妥、烯丙异丙巴比妥、异戊巴比妥、速可眠、SKF525、异丙嗪、去氧安定、氯丙嗪、利眠宁等9种镇静安眠类药物萃取后进行GC/MS检测,并对实验条件进行优化。结果经用ASE-GC/MS法检测空白添加血样,9种药物均获得很好的分离和检出。最佳萃取温度为110℃,萃取时间为3min,萃取溶剂为苯。9种药物在0.5~5.0μg/mL范围内线性关系良好,相关系数在0.984 2~0.998 1之间,检出限在1.0μg/mL左右。回收率在80.1%~106.3%之间,变异系数(CV)均小于3.62%。结论本文方法操作简便、快捷,回收率高,可用于常见镇静安眠类药物的检测。     

尿样中安眠酮代谢物的分析

安眠酮是一种作用时间快、半衰期长的低毒性镇静催眠药物,长期服用有一定的成瘾性,目前国际上已将此药列为滥用药品,控制其生产和使用。由于安眠酮的代谢周期长,在体内容易积累,其代谢物     

毛发中GHB的检测及评价

目的探索毛发中外源性GHB的检测及判断的可行性,为涉GHB的鉴定提供方法和依据。方法建立毛发中GHB的GC/MS分析方法,并通过动物实验,考察毛发中内源性GHB的质量分数范围、外源性GHB在毛发中的时间过程以及给药剂量、毛发颜色与毛发中GHB的质量分数关系。结果豚鼠和中国人黑色毛发中内源性GHB质量分数分别为(3.01±1.41)ng/mg(n=28)和(1.02±0.27)ng/mg(n=20);摄GHB后毛发中GHB质量分数明显增加且与给药剂量呈正相关性;GHB在毛干中呈窄带分布;深色毛发中GHB质量分数高于浅色毛发。结论毛发中GHB的检测适用于GHB滥用和中毒的法医毒物学鉴定;根据毛发中的GHB质量分数和毛发分段分析可判断GHB的来源。     

毛发中的毒物分析

在毒物分析中，尤其是法医学领域，毛发以其化学性质稳定，容易获得及贮存，不易受外界杂质于扰等优点而颇具研究价值．1954年,Goldblum等首次报道了利用紫外分光光度法检测豚鼠毛发中的巴比妥类含量[1]．近五十年来，毛发中毒物分析越来越受到重视，特别是七十年代末至今，毛发分析技术已基本趋于成熟．本文拟就毛发毒物分析中的毛发处理、检测方法等一些主要问题作一综述．1毒物与毛发的结合机制毛发根部的毛腺体（Follicle）与血液循环沟通，血液中的药（毒）物经血液循环输送到毛腺体，随着时间的推移，毛发成长为毛髓质（medull），外…     

Testing for zopiclone in hair application to drug-facilitated crimes

The use of a drug to modify a person's behaviour for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, robbery) has caused alarm in the general public. The drugs involved can be difficult to detect due to low dosages or chemical instability. They possess amnesic properties and can be quickly cleared from the body fluids. In these situations, blood or even urine can be of poor interest. This is the reason why this laboratory developed an original approach based on hair testing by LC-MS/MS. Zopiclone (Imovane), due to its short half-life associated with rapid hypnotic activity, is considered as a compound of choice to sedate victims. To document the detection of zopiclone in hair, we first tested specimens obtained from two volunteers who had ingested a single 7.5 mg Imovane tablet, and from repetitive consumers of zopiclone. After pH 8.4 buffer incubation and extraction with methylene chloride/diethyl ether (80/20 (v/v)), hair extracts were separated on a Xterra MS C18 column using a gradient of acetonitrile and formate buffer. Zopiclone and diazepam-d5, used as internal standard, were detected by tandem mass spectrometry. A single exposure to zopiclone was detectable in the first hair segment of two volunteers at concentration of 5.4 and 9.0 pg/mg, respectively. Hair from repetitive consumers tested positive for zopiclone at concentrations of 37 and 66 pg/mg. Hair analysis was applied to two authentic criminal cases. In the first one, zopiclone tested positive in the corresponding hair segment at 4.2 pg/mg, in accordance with a single exposure to the drug. In the other expertise, zopiclone was detected in the two segments analyzed, at 21.3 and 21.5 pg/mg, making unlikely the hypothetical single exposure to zopiclone.     

Identification of alprazolam in hair in two cases of drug-facilitated incidents

The use of a drug to modify a person's behaviour for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, robbery) has caused alarm by the general public. Among the drugs that can be used, alprazolam (Xanax), an anxiolytic benzodiazepine, has been seldom observed. To document two cases involving this drug, we have developed an approach based on hair testing by LC-MS/MS. After pH 8.4 buffer incubation and extraction with methylene chloride/diethyl ether (80/20, v/v), hair extracts were separated on a XTerra MS C18 column using a gradient of acetonitrile and formate buffer. Alprazolam and diazepam-d5, used as internal standard, were detected by electrospray tandem mass spectrometry. In the first criminal case, alprazolam tested positive in two consecutive 2 cm hair segments at 4.9 and 2.4 pg/mg, from a 12-year-old girl, assaulted by her father who had sedated her three or four times. In the other case, alprazolam was detected in four consecutive 1cm hair segments at 3.1-0.4 pg/mg, obtained from an adolescent who had been forced to prostitute herself.     

Correlation of the incidence of cocaine and cocaethylene in hair and postmortem biologic samples

Hair samples are useful as a matrix for drug testing because drugs can be detected in hair for longer periods than in blood or urine. The authors report a prospective comparison of the detection of cocaine and cocaethylene in routine postmortem biologic specimens to the detection of cocaine and cocaethylene in hair. The authors collected hair samples from various areas of the head in 53 autopsy cases, prepared them, and analyzed them by gas chromatography/mass spectrometry (GC/MS) for cocaine and cocaethylene. The authors compared the results of hair analysis with the results of toxicologic analysis performed on routine postmortem samples by enzyme multiplied immunoassay technique and GC/MS. Cocaine was found in either biologic fluids or in hair in 16 of 53 samples tested. Nine samples were positive for cocaine in both biologic fluids and hair. Five samples contained cocaine only in biologic fluids, and two contained cocaine only in hair. Cocaethylene was present in two cases. Drug screening of hair provides additional information in some autopsy cases, but the authors have not made hair analysis a routine practice. It may prove useful to save hair samples in all cases for later analysis if warranted by additional history or autopsy findings.     

Identification of selected psychopharmaceuticals and their metabolites in hair by LC/ESI-CID/MS and LC/MS/MS

Hair samples of patients of psychiatry and hair samples of suicide cases were analysed by liquid-chromatography/ionspray-mass spectrometry (LC/MS) for antidepressants and neuroleptics. Electrospray ionisation (ESI) with in-source collision induced dissociation (ESI/CID) and tandem-mass spectrometry (MS/MS) were used for drug and metabolite identification. Mass spectra library searching was performed using an ESI/CID mass spectra library and a MS/MS spectra library. Furthermore, extracted ion chromatograms were used for the detection of N-desmethyl-metabolites, which were also identified by their fragment-ion spectra. Three examples using these methods are shown: The tricyclic antidepressant maprotiline, the selective serotonin receptor inhibitor (SSRI) citalopram and their desmethylmetabolites as well as the neuroleptic pipamperone were detected and identified in hair extracts. For extraction powdered hair was treated by ultrasonication in methanol and solid-phase extraction was used for sample clean-up prior to LC/MS or MS/MS analysis. These examples demonstrate the power of LC/MS and LC/MS/MS for the detection and identification of drugs in hair extracts using full-scan mode and ESI/CID with library searching or using highly selective LC/MS/MS-analysis with library searching or in multiple reaction monitoring mode.     

New trends in hair analysis and scientific demands on validation and technical notes

This review focuses on basic aspects of method development and validation of hair testing procedures. Quality assurance is a major issue in drug testing in hair resulting in new recommendations, validation procedures and inter-laboratory comparisons. Furthermore recent trends in research concerning hair analysis are discussed, namely mechanisms of drug incorporation and retention, novel analytical procedures (especially ones using liquid chromatography-mass spectrometry (LC-MS) and alternative sample preparation techniques like solid-phase microextraction (SPME)), the determination of THC-COOH in hair samples, hair testing in drug-facilitated crimes, enantioselective hair testing procedures and the importance of hair analysis in clinical trials. Hair testing in analytical toxicology is still an area in need of further research.     

Prolonged excretion of 7-aminoclonazepam in urine after repeated ingestion of clonazepam: A case report

Urinary analyses of the metabolite 7-aminoclonazepam (7-AC) can be helpful in monitoring drug abuse and in the context of suspected drug-facilitated sexual assaults (DFSA). Only two studies have reported detection times of 7-AC in urine after a single dose of clonazepam, and no previous studies have reported detection times after repeated ingestions of clonazepam. This report describes along detection time of 7-AC in urine in the case of a 28-year-old woman with a two year history of daily drug abuse of heroin and clonazepam, who was admitted to a detoxification unit. Urinary samples were delivered every morning for 9 days. Screening analysis in urine was performed by immunoassay, and confirmation analysis by LC-MS/MS. 7-AC was detected for 9 days, and the concentration at day 9 was still high (97ng/ml), compared to previously reported data. These results indicate that after repeated ingestions of clonazepam, 7-AC can possibly be detected for about 2-3 weeks after cessation, applying cut-off levels commonly used in drug testing programs and DFSA cases.     

Deposition of 7-aminoflunitrazepam and flunitrazepam in hair after a single dose of Rohypnol

In recent years, there has been a notable increase in the number of reports on drug-facilitated sexual assault. Benzodiazepines are the most common so-called "date-rape" drugs, with flunitrazepam (Rohypnol) being one of the most frequently mentioned. The aim of this study was to determine whether flunitrazepam and its major metabolite 7-aminoflunitrazepam could be detected in hair collected from ten healthy volunteers after receiving a single 2 mg dose of Rohypnol using solid phase extraction and NCI-GC-MS. Such data would be of great importance to law enforcement agencies trying to determine the best time interval for hair collection from a victim of drug-facilitated sexual assault in order to reveal drug use. Ten healthy volunteers (eight women and two men, 21 to 49 years old) participated in the study. The following hair samples were collected from each volunteer: one before flunitrazepam administration, and 1, 3, 5, 14, 21, and 28 days after. In five volunteers, 7-aminoflunitrazepam was detected 24 h after flunitrazepam administration and remained in hair throughout the entire 28-day study period (0.6-8.0 pg/mg). In two cases, 7-aminoflunitrazepam appeared in hair 21 days after drug intake (0.5-2.7 pg/mg), and in two subjects 14 days later (0.5-5.4 pg/mg). In one volunteer, 7-aminoflunitrazepam was detected on day 14 and 21 but concentrations were below the quantitation limit. Flunitrazepam was detected in some samples but all concentrations were below the quantitation limit (0.5-2.3 pg/mg).     

Determination of ethyl glucuronide in human hair by SPE and LC-MS/MS

A method for the sensitive and selective determination of ethyl glucuronide (EtG) in hair has been developed using solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Washed and cut hair segments were extracted by ultrasonication (3h, 50 degrees C) and the extracts were cleaned-up with aminopropyl SPE columns. LC-MS/MS analysis was performed using a polar-endcapped phenyl-hexyl-RP-phase with negative mode electrospray ionisation (ESI) using a triple quadrupole mass spectrometer (Sciex API 365) with a turboionspray source and post-column addition of acetonitrile for enhanced sensitivity. The MS/MS transitions monitored were m/z 221 -->75 for EtG and 226 -->75 for D(5)-EtG as an internal standard. The method was selective and sensitive, with a detection limit of 51 pg/mg hair at a signal-to-noise ratio of 3:1. The mean recovery was 96%, with an intra- and inter-day precision of less than 11.7% at a concentration of 200 pg/mg. The linearity was assessed in the range of 25-2000 pg/mg hair, with a correlation coefficient of 0.997. The method was successfully applied to 97 human hair samples which were taken at autopsies from persons with known alcoholism or were obtained from alcoholics who were hospitalized for ethanol withdrawal, from social drinkers and from children having not consumed any alcohol. Although, approximately two-third of the alcoholics showed EtG concentrations in hair of higher than 51 pg/mg (up to >4000 pg/mg), in one-third the EtG concentration was below the detection limit. However, only in one of five hair samples of "social drinkers", the EtG concentration was above the detection limit (51 pg/mg). No EtG has been detected in the hair of children. These investigations demonstrate that heavy alcohol consumption may be but not necessarily has to be detectable by EtG analysis in hair.     

基质辅助激光解吸飞行时间质谱分析生物样品中甲基苯丙胺

目的建立尿样和头发中甲基苯丙胺的基质辅助激光解吸飞行时间质谱（matrix-assisted laser desorption/ionization time of flight mass spectrometry,MALDI-TOF-MS）分析方法。方法尿样采用液液提取,头发经0.1mol/L盐酸水解后采用液液提取,以碳纳米管为基质应用MALDI-TOF-MS法检测。结果尿样中甲基苯丙胺的最低检测限（LOD）为0.5μg/mL,线线范围为线性范围为0.5～100μg/mL（R2=0.9970）;毛发中甲基苯丙胺的最低检测限（LOD）为0.4ng/mg,线性范围为0.4～60ng/mg（R2=0.9976）,对送检案例中尿样和头发检材进行检测,效果良好。结论本方法适用于尿样和头发中甲基苯丙胺的分析,与传统气相色谱质谱联用和液相色谱-质谱联用相比,分析速度更快,适合大批量样品同时分析。