氯胺酮滥用的研究进展

氯胺酮为非竞争性NMDA受体阻断剂,作为一种分离性麻醉药应用于临床,其作用机制复杂,由于其具有一定的致幻作用而被滥用于各种娱乐场所,是目前药物滥用中的一个新问题。本文在阐述氯胺酮的药理学及毒理学特性的基础上,复习了氯胺酮与NMDA受体、多巴胺受体等神经生物学相关受体的相互作用,综述氯胺酮滥用的现状、滥用的可能生理机制及其滥用后的检测方法等方面的研究进展。     

氯胺酮的滥用及检测现状

氯胺酮是一种高效麻醉剂,应用于人和动物的手术过程中,由于其具有一定的精神副作用而被滥用于娱乐场所。氯胺酮在体内先经N去甲基作用产生去甲氯胺酮,再脱氢生成去氢去甲氯胺酮。本文综述了氯胺酮的滥用现状和检测现状,目前文献报道的检测分析方法主要有TLC、GC/NPD、GC/MS和LC/MS等。     

我国制贩氯胺酮犯罪综述

氯胺酮在我国大陆的滥用起步较晚。上世纪90年代初,港澳台及东南亚地区毒品问题发生变化,吸食者开始尝试新兴的精神药物,其中包括氯胺酮(常称作“K粉”或“K仔”)。1999年,香港首次查获氯胺酮。2000年,氯胺酮已广受香港青少年滥用者的欢迎,其滥用程度已超过MDMA。从2001年开始,氯胺酮跃升为香港滥用药物之最。随着粤港澳三地经济     

氯胺酮成瘾机制的研究进展

氯胺酮为苯环己哌啶（PCP）衍生物,是非竞争性N-甲基-D-天门冬氨酸（NMDA）受体桔抗剂。除作为临床上常用的静脉麻醉药外,氯胺酮还具有一定的致幻作用和成瘾性,非法滥用氯胺酮的人数呈现快速增长趋势。本文根据氯胺酮的药理及毒理学特性与目前公认的药物成瘾机制．从与药物成瘾机制有关的强化效应和奖赏系统、解剖结构、相关受体及个体差异等方面,对氯胺酮成瘾的可能机制作一综述。     

氯胺酮合并多物质滥用的毒性损害作用相关研究进展

氯胺酮是一种新型成瘾性物质,近年来在我国氯胺酮合并多物质滥用的现状日趋严峻,其中青少年人群的滥用尤其值得关注。氯胺酮合并多物质滥用后,往往会有更为严重的精神损害、中枢神经系统损害以及心脏、肺、肝、肾等器官的毒性损害。本文拟从氯胺酮的基本性质、氯胺酮与其他成瘾性物质尤其是乙醇联合滥用的现状及趋势及其所导致的精神、中枢神经系统、心脏、肺、肝脏、肾脏等器官损害等,结合国内外研究进展作简要综述。     

生物检材中氯胺酮及其代谢物的检测

近年来氯胺酮的滥用越来越普遍,建立快速、准确的检测方法越来越重要。氯胺酮在生物体内的代谢物主要有去甲氯胺酮、脱氢去甲氯胺酮等。目前,常用的生物检材有血液、尿液、毛发等。常用的检测方法有气相色谱法、气相色谱-质谱联用法、高效液相色谱法、液相色谱-质谱联用法、高效毛细管电泳法等。本文参考近年来的相关文献对生物检材中氯胺酮及其代谢物的检测方法作一综述,为法医毒物分析等相关领域提供参考。     

尿中氯胺酮及其代谢物检测的研究

目的建立氯胺酮滥用者尿中氯胺酮及其代谢物检测方法。方法尿液用有机溶剂液-液萃取,气相色谱/氮磷检测器、电子捕获检测器、氢火焰检测器和气-质联用仪测定。结果确认了尿液中氯胺酮的主要代谢物,尿液中氯胺酮及去甲氯胺酮的最小检测限均为2ng/mL,脱氢去甲氯胺酮的最小检测限为5ng/mL。结论所建方法快速、灵敏、准确,能够满足氯胺酮滥用者尿液检测的需要。     

家兔唾液与血液中氯胺酮浓度的相关性

目的研究家兔唾液中氯胺酮及代谢物去甲氯胺酮浓度与血药浓度的相关性。方法实验家兔分为氯胺酮灌胃组（6只）、静脉注射组（6只）和对照组（6只）,分别于染毒前、后不同时间点收集唾液和血液。采用气相色谱/质谱联用（GC/MS）全扫描定性、气相色谱（GC）定量分析样品中氯胺酮及去甲氯胺酮的浓度。采用双变量Pearson相关分析研究唾液中药物浓度和血药浓度的相关性。结果氯胺酮灌胃组和静脉注射组给药后各时间点氯胺酮及去甲氯胺酮在唾液和血液中的浓度相关系数（r）范围为0.80-0.95。结论氯胺酮及去甲氯胺酮在唾液和血液中的浓度均有良好的相关性,根据唾液药物浓度推断血药浓度可用于氯胺酮滥用的法医学鉴定。     

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。     

GC／MS定性K粉及其中间体的应用

k粉商品名为氯胺酮(ketamine),本品属静脉麻醉药.它能选择性地阻断痛觉,麻醉时呈浅睡状态,意识模糊,长期使用可产生精神依赖性.近几年国内滥用氯胺酮者急剧增加,特别是经常出入迪厅、歌舞厅的年轻人群体,因吸食氯胺酮或服用含有氯胺酮的"摇头丸"、"迷奸药"而致中毒甚至死亡的案件逐年上升[1].氯胺酮于2004年,被国家列人管制的二类精神药品.     

Profiles of urine samples from participants at rave party in Taiwan: prevalence of ketamine and MDMA abuse

Drug abuse patterns are different due to cultural, social and geographical differences. Methamphetamine (MA) is the most important drug of abuse in Taiwan followed by opiates. Recently, there has been an increase of ketamine and MDMA abuse in disco dancing clubs. Here, we report the patterns of drug abuse by the participants in a metropolitan city disco-dancing club and the general public in Taiwan. The positive rates of common drugs of abuse detected in samples collected from participants in a dancing club were as follows: MDMA, 75.7%; ketamine, 47.0%; MA, 41.6%; opiates, 0%. Marijuana and cocaine were detected at much lower rates (3.4 and 4.7%, respectively). Ketamine and one of the amphetamines were detected together in 42.9% of the samples. The positive rates in samples collected from police detainees suspected of drug abuse in the general public were as follows: MA, 76.0%; OPA, 37.0%; MDMA, 6.0%; ketamine, 2.0%.     

Use of SPE and LC/TIS/MS/MS for rapid detection and quantitation of ketamine and its metabolite, norketamine, in urine

Ketamine (K) has become more and more popular for drug abuse in recent years. A lot of pre-treatment work such as extraction and derivatizing increase difficulties in the tests for ketamine in biological specimens. A rapid method to detect and quantitate ketamine and its metabolite norketamine in urine used deuterated dilution followed by solid phase extraction and liquid chromatography/TurboIonSpray/tandem mass spectrometry (LC/TIS/MS/MS) is described. Control recovery for both low and high concentrations can reach to 90%. Ten ketamine positive urines were examinated by this method. Concentrations ranged from 114 to 2925 ng/mL and from 453 to 9805 ng/mL for norketamine. The method was sensitive, specific, accurate and provided easy operation to detect and quantitate ketamine and its metabolites in urine.     

氯胺酮体内分布综述

氯胺酮作为一种重要的麻醉药品在临床上有着广泛的应用。近年来,其非法滥用问题日益凸显,随之而来的犯罪数量亦呈不断增长趋势。本文对氯胺酮在活体内的分布以及死后尸体内再分布等受温度、药物相互作用、邻近组织器官相互作用、尸体保存条件等因素影响进行了综述。     

Simultaneous analysis of psychotropic phenylalkylamines in oral fluid by GC-MS with automated SPE and its application to legal cases

Phenylalkylamine derivatives, such as methamphetamine (MA), amphetamine (AM), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), phentermine (PT), fenfluramine (FFA) and phenmetrazine (PM), and ketamine (KT) are widely abused recreational or anorectic drugs in Korea and are regulated under the Controlled Substance Act in Korea. Phenylalkylamines and ketamine analysis is normally performed using both urine and hair samples but there is no established method for the simultaneous analysis of all these phenylalkylamines and ketamine in oral fluids. Oral fluid is easy to collect/handle and can provide an indication of recent drug abuse. In this study, to confirm the presence of phenylalkylamine derivatives and ketamine in oral fluid after screening with an immunoassay, an analytical method using automated solid phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS) was developed and fully validated according to international guidelines. The applicability of the assay was demonstrated by analyzing of authentic oral fluid samples and the results of oral fluid analysis were compared with those in urine and hair to to evaluate the feasibility of oral fluid in forensic cases. The recovery of phenylalkylamines and ketamine from oral fluid collection devices was also assessed. Oral fluid specimens from 23 drug abuse suspects submitted by the police were collected using Salivette (Sarstedt, Nümbrecht, Germany), Quantisal (Immunalysis, Pomona, CA) or direct expectoration. The samples were screened using a biochip array analyzer (Evidence Investigator, Randox, Antrim, UK). For confirmation, the samples were analyzed by GC-MS in selected-ion monitoring (SIM) mode after extraction using automated SPE (RapidTrace, Zymark, MA, USA) with a mixed-mode cation exchange cartridge (CLEAN SCREEN, 130 mg/3 ml, UCT, PA, USA) and derivatization with trifluoroacetic anhydride (TFA). The results from the immunoassay were consistent with those from GC-MS. Twenty oral fluid samples gave positive results for MA, AM, PT and/or PM among the 23 cases, which gave positive results in urine and/or hair. Although large variations in the MA, AM, PT and PM concentrations were observed in three different specimens, the oral fluid specimen was useful for demonstrating phenylalkylamines and ketamine abuse as an alternative specimen for urine.     

Rapid determination of ketamine in urine by liquid chromatography-tandem mass spectrometry for a high throughput laboratory

In recent years, the abuse of ketamine had gained popularity in rave parties in Hong Kong. The Urinalysis Unit of the Government Laboratory of Hong Kong faced a tremendous increase in workload for ketamine analysis. The number of tests performed rose from 10 in 1999 to 15,000 in 2002. As a fully validated immunoassay test for ketamine was not available in the market, most laboratories analyzed ketamine by chromatographic techniques after liquid-liquid extraction. However, these methods reported in the literature are not suitable for high throughput laboratories. Hence, a rapid screening/confirmation method for ketamine by liquid chromatography-tandem mass spectrometry (LC-MS-MS) with a detection limit of 5 ng/ml was developed. After automated solid-phase extraction (SPE), the urine extract was analyzed for ketamine by a 2.5-min chromatographic run, the estimated recovery was 89% and the precision was 11% R.S.D. at 20 ng/ml. With the aid of an in-house developed computer program, the results were presented in spreadsheet format for easy checking. The method has been applied to our laboratory for routine ketamine analysis and a maximum of 200 samples per day can be achieved.     

Assessment of age and sex by means of DXA bone densitometry: application in forensic anthropology

An effective way to reveal the history of drug abuse is to determine the parental drug and its metabolites in hair. Here, a quantitative HPLC-Chip-MS/MS method was developed for simultaneous measurement of ketamine and its metabolite norketamine in human hair. Ketamine and norketamine were extracted from hair by acid hydrolysis, and then enriched by organic solvent extraction. The chromatographic separation was achieved in 15 min, with the drug identification and quantification by a tandem mass spectrometer. The linear regression analysis was calibrated by deuterated internal standards with a R(2) of over 0.996. The limit of detection (LOD) and the limit of quantification (LOQ) for ketamine and norketamine were 0.5 and 1 pg/mg of hair, respectively. The standard curves were linear from the value of LOQ up to 100 pg/mg of hair. The validation parameters including selectivity, accuracy, precision, stability and matrix effect were also determined. In conclusion, this method was able to reveal the present of ketamine and norketamine with less hair from the drug abusers, and which had the sensitivity of ～1000-fold higher than the conventional method. In addition, the amount of ketamine and norketamine being detected in different hair segments would be useful in revealing the historical record of ketamine uptake in the drug abusers.     

Patterns of physical and sexual abuse for men and women in dating relationships: A descriptive analysis

A random sample of students at a large Midwestern University was selected in order to examine whether and how physical and sexual abuse were related to each other for men and women, whether abuse in one relationship was independent of abuse in other relationships, and how victims responded to abusive incidents. The results revealed several important patterns. When comparing the frequency of physical and sexual abuse for men and women, it was found that sexual abuse was more common than physical abuse, but only for women. Additionally, women experienced more sexual abuse than men. While men and women did not experience physical abuse in other relationships at more than chance levels, women who sustained sexual abuse in one relationship were more likely to sustain sexual abuse in other relationships. Furthermore, while sustaining physical and sexual abuse were not associated with one another for men, there was a weak association for women. Finally, victims of abuse were more likely to tell their friends they had been abused than report it to criminal justice authorities.Paper presented at the 1987 American Society of Criminology Meetings.     

家兔血液和尿液中氯胺酮浓度的相关性

目的研究家兔尿液中氯胺酮及代谢物去甲氯胺酮浓度与血药浓度的动态相关性。方法实验家兔分为氯胺酮灌胃组、静脉注射组和对照组,分别于染毒前和染毒后不同时间点收集尿液和血液。气相色谱/质谱联用(GC/MS)全扫描定性、气相色谱(GC)定量分析血液和尿液样品中氯胺酮及去甲氯胺酮的浓度。采用双变量Pearson相关分析研究尿液中药物浓度和血药浓度的相关性。结果氯胺酮灌胃组和静脉注射组给药后各时间点氯胺酮及去甲氯胺酮在尿液和血液中的浓度相关系数范围在0.11～0.69之间。结论氯胺酮及去甲氯胺酮在尿液和血液中的浓度相关性较差,尿液药物浓度并不能直接反映血药浓度,因此用尿液中氯胺酮浓度推断血药浓度时应慎重考虑。