Evaluation of portable gas chromatography–mass spectrometry (GC–MS) for the analysis of fentanyl,fentanyl analogs,and other synthetic opioids

Potent synthetic opioids including fentanyl and its analogs are frequently encountered in the field and require detection and identification by first responders to maintain the safety of drug abusers, first responders, health-care providers, and the public at large. Due to the low concentration at which these substances may be encountered and the complicating matrices within which they may be dispersed, the use of portable gas chromatography–mass spectrometry (GC–MS) for their identification in the field offers great potential value. This research established that portable GC–MS is a useful method for the detection and identification of a large number of synthetic opioids, especially fentanyl and its analogs. In this study, 250 synthetic opioids and related substances including 210 fentanyl analogs were analyzed using portable GC–MS. It was concluded that 225 of the 250 (90.0%) opioids analyzed were successfully detected onboard at the time of analysis and identified as either the substance (55.2%) or an analog (34.8%). These outcomes have equivalent benefit for the field analysis of illicit drugs due to both initiating the same subsequent actions by first responders.     

生物检材中苯丙胺类兴奋剂和氯胺酮的LC-MS/MS分析

目的建立生物检材中苯丙胺类兴奋剂和氯胺酮的液相色谱-串联质谱(LC-MS/MS)分析方法。方法生物检材包括血液、尿液和毛发,采用稀释法和液液提取的前处理方法,应用两个不同的液相柱,优化LC-MS/MS分析方法,并考察了血液和尿液基质的离子抑制作用。结果同时分析苯丙胺和MDA,液相1在3m in内完成,液相2可用于确认分析或复杂基质分离。尿液稀释法检材用量少,前处理简便快速。毛发中苯丙胺类兴奋剂和氯胺酮的最低检测限(LOD)为0.005~0.05ng/mg。对送检案例检材产妇头发和胎毛进行苯丙胺类兴奋剂和氯胺酮的分析。结论本方法可用于生物检材中苯丙胺类兴奋剂和氯胺酮的同时分析,血、尿等生物检材的离子抑制作用是影响本方法灵敏度的主要原因。     

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。     

Nail analysis for the assessment of caffeine abuse in Northwest China: A population-based study

Caffeine is the most widely consumed psychoactive agent worldwide and has the potential for abuse, but studies monitoring caffeine abuse in China are scarce. This study aims to estimate the prevalence of caffeine abuse in northwest China and investigate the correlation between caffeine and other drugs in hair and nails using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Fingernail clippings were collected from 376 participants in northwest China to detect caffeine and 13 other illicit psychoactive drugs and their metabolites. Paired hair and nail samples were collected from 39 participants to investigate the correlation between caffeine and other drugs in hair and nails. The samples were decontaminated, pulverized, and extracted by a high-throughput nail sample preparation method and analyzed by UPLC-MS/MS. The results showed a risk of caffeine abuse in northwest China, with concentrations ranging from 0.43 to 10.6 ng/mg for healthy volunteers, 0.49–246 ng/mg for caffeine abusers, and 0.25–363 ng/mg for drug addicts in community rehabilitation centers. Caffeine was detected together with other illicit psychoactive drugs and their metabolites. Furthermore, positive detection correlations were found between hair and nail samples. This study provides a current perspective on caffeine abuse in northwest China and demonstrates the practical use of UPLC-MS/MS for the simultaneous detection of caffeine and 13 illicit psychoactive drugs and their metabolites in hair and nails. The results highlight the potential of nails as a supplementary matrix when hair samples are unavailable and emphasize the need for handling caffeine carefully given its potential for abuse.     

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.     

Windows of detection of zolpidem in urine and hair: application to two drug facilitated sexual assaults

A LC-MS/MS method for the detection of zolpidem in hair was developed to detect this drug after a single dose in possible drug facilitated sexual assaults. To determine the window of detection of zolpidem in both urine and hair, three volunteers received a 10 mg dose. Urine specimens were collected each 12 h for 144 h. Hair was sampled 3-5 weeks after exposure. Hair and urine extracts were separated on a Xterra MS C18 column using a gradient of acetonitrile and formate buffer. For each compound, detection was related to two daughter ions. Zolpidem was detected for up to 60 h in urine with peak concentrations obtained at 12 h. A single exposure to zolpidem was detected in hair at concentrations ranging from 1.8 to 9.8 pg/mg. Hair analysis was applied to two possible criminal cases. In the first case, zolpidem tested positive in the corresponding hair segment at 4.4 pg/mg. In the other case, zolpidem was detected in all the segments analyzed, demonstrating likely previous drug use in addition to recent exposure associated with a positive blood result.     

Prevalence and blood concentrations of benzodiazepines and opioids in opioid-positive death investigations in Ontario,Canada, from 2017 to 2021

The aim of this study was to investigate the incidence of benzodiazepines in opioid-positive death investigations, including trends in frequency and combination of drugs, as well as demographic data and blood concentrations, where available. Additionally, naloxone concentrations in polysubstance compared to opioid-only cases were analyzed. This was a retrospective study that consisted of all post-mortem toxicology cases in Ontario, Canada, from January 01, 2017, to December 31, 2021, with an opioid finding in any analyzed autopsy specimen. There were 11,033 death investigations identified. The overall rate of benzodiazepine co-involvement was 54.5%. Males accounted for the majority of cases (71%), and the most affected age group was 30- to 39-year-olds. The most frequently detected opioid was fentanyl and the most frequently detected benzodiazepine was etizolam, which was also the most frequently observed opioid/benzodiazepine combination. Findings related to differences in concentrations of opioids when naloxone was also present were mostly non-significant, except for methadone. The rate of benzodiazepine detection with opioids grew faster than opioid detections overall, potentially due to the increasingly toxic drug supply. Detection of novel psychoactive drugs fluctuated more unpredictably than opioids and benzodiazepines associated with clinical use. These findings can help inform policy decisions by public health agencies in exploring harm reduction efforts, for example, education and drug-checking services.     

Benzoylecgonine (cocaine metabolite) detection in hair samples of jail detainees using radioimmunoassay (RIA) and gas chromatography/mass spectrometry (GC/MS)

Benzoylecgonine (BE) was detected in hair samples using nonproprietary extraction methodology and modifications of well-established radioimmunoassay (RIA) screening/quantitative gas chromatography/mass spectrometry (GC/MS) confirmation procedures. Samples collected anonymously from a population of 48 jail detainees weighed between 5.3 and 61.2 mg. All of the 22 hair samples which had RIA results indicating the presence of BE or immunologically similar substances above a cutoff amount of 1.25 ng/sample (50 ng/mL) were confirmed by GC/MS. Several varieties of hair color and texture were tested, although in each general category there were samples which contained BE as well as other samples which did not reveal detectable amounts of BE. The range of concentrations in 22 hair extracts that screened positive were 0.26 to 18 ng/mg hair as determined by GC/MS. In comparison with other reports of cocaine-related substances in hair, these data show consistent concentrations.     

Hair analysis: self-reported use of "speed" and "ecstasy" compared with laboratory findings

Drug use histories were collected from 100 subjects recruited from the "dance scene" in and around Glasgow, Scotland. In addition, each subject donated a hair sample which was analyzed by gas chromatography/mass spectrometry (GC/MS) for amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MD MA) and 3,4-methylenedioxyethylamphetamine (MDEA). The hair samples were analyzed in two 6 cm segments or in full, ranging from 1.5 to 12 cm depending on the length of the hair. Approximately 10 mg of hair was ground to a fine powder before treatment with beta-glucuronidase/aryl sulfatase. A solid-phase extraction procedure was carried out followed by derivatization with pentafluoropropionic anhydride (PFPA). All extracts were analyzed by gas chromatography/mass spectrometry (GC/MS). Of the 139 segments analyzed, 77 (52.5%) were positive for at least one of the five amphetamines. The drug concentrations found in the hair were compared with the self-reported drug histories. A concordance of greater than 50% was found between the self-report data and levels detected in hair. However, no correlation was found between the reported number of "ecstasy" tablets consumed and the drug levels detected in hair. An increase in the average drug levels measured was observed from low to high use (number of "ecstasy" tablets/month). A large number of false negatives and a low number of false positives were observed.     

头发中5-MeO-DiPT等12种新型色胺类致幻剂的UPLC-MS/MS分析方法研究

目的建立同时分析头发中5-MeO-DiPT等12种新型色胺类致幻剂的超高效液相色谱-串联质谱(UPLC-MS/MS)方法。方法以赛洛西宾-d4和赛洛新-d10为内标,20 mg头发样品加入1 mL提取液(含内标2 ng/mL的0.1%甲酸水溶液)后冷冻研磨,离心取上清液,经Waters Acquity^TM UPLC HSS T3色谱柱分离,采用多反应监测模式同时测定12种新型色胺类致幻剂。结果头发样品中12种色胺类新精神活性物质的检出限为1~10pg/mg,定量限为3~50pg/mg。在相应浓度范围内,12种色胺类新精神活性物质均具有良好的线性关系,相关系数大于0.99。本方法准确度为91.3%~113.5%,日间和日内精密度(RSD)均小于15%,回收率大于80%,无明显基质效应。结论该方法前处理简单、灵敏度高、选择性好,适用于法医毒物分析中新型色胺类致幻剂的鉴定。     

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。     

Field-portable detection of fentanyl and its analogs: A review

The need to detect fentanyl and its analogs in the field is an important capability to help prevent unintentional exposure or overdose on these substances, which may result in death. Many portable methods historically used in the field by first responders and other field users to detect and identify other chemical substances, such as hazardous materials, have been applied to the detection and identification of these synthetic opioids. This paper describes field portable spectroscopic methods used for the detection and identification of fentanyl and its analogs. The methods described are automated colorimetric tests including lateral flow assays; vibrational spectroscopy (mid-infrared and Raman); gas chromatography–mass spectrometry; ion mobility spectrometry, and high-pressure mass spectrometry. In each case the background and key details of these technologies are outlined, followed by a discussion of the application of the technology in the field. Attention is paid to the analysis of complex mixtures and limits of detection, including the required spectral databases and algorithms used to interrogate these types of samples. There is also an emphasis on providing actionable information to the (likely) non-scientist operators of these instruments in the field.     

单次摄药毛发分析的研究进展

“迷药犯罪”是指对被害人下药后实施性侵犯、抢劫、诈骗等犯罪行为。单次摄入的镇静催眠类或迷幻类药物在体内迅速代谢,故难以用血液、尿液检测等常规方法来提供摄药证据,而毛发分析的长检测窗特点在解决这类案件时具有重要的价值。单次摄药的毛发分析要求检测方法有很高的灵敏度,需要用二级质谱检测器进行分析,且从头发采样、去污、水解、提取、分析的各环节均应注意防止污染,避免出现假阳性结果。采集的头发必须进行分段分析,除检测对应案发时间的头发段外,还应把其它头发段的检测结果作为对照,据此对分析结果作出严谨、科学的解释。目前已建立了31种镇静催眠药、6种苯丙胺类衍生物、GHB、硫喷妥及其代谢物戊巴比妥以及乙醇代谢物EtG等的检测方法,可以应用于实际案件的毛发分析。     

GC/MS、GC/NPD法检测毛发中的氯胺酮

目的采用液-液萃取、衍生化和GC/MS、GC/NPD方法,进行毛发中氯胺酮定性定量分析。方法选择4-苯基丁胺为内标,毛发样本用NaOH、HCl及芳基硫酸酯酶/β-葡萄糖醛酸酶等3种方式进行水解,再进行衍生化后,采用GC/MS和GC/NPD方法定性定量分析。对不同水解和衍生化条件以及提取溶剂进行比较优化,并考察方法精密度、稳定性和检出限。结果方法的提取回收率大于95%,精密度和样品稳定性良好,日内和日间标准偏差小于6%;采用GC/NPD和GC/MS直接分析毛发中的氯胺酮,检出限为0.2ng/mg和2.0ng/mg,线性范围为10.0～250.0ng/mg,相关系数均大于0.99;采用酰化衍生化后分析,GC/NPD和GC/MS检出限分别提高至0.1ng/mg和0.2ng/mg。结论该方法回收率高、检测限低,可以用于毛发中氯胺酮的定性定量分析检验。     

Toxicology and characteristics of deaths involving zolpidem in new South wales, australia 2001-2010*

Abstract: All cases presenting to the New South Wales Department of Forensic Medicine between January 1, 2001 and September 31, 2010 in which zolpidem was detected, were retrieved. A total of 91 cases were identified. The mean age was 49.4 years, 65.9% were male, and 61.5% were suicides. Zolpidem was a factor contributing to death in 35 (37.3%) cases, of which 31 (34.1%) involved zolpidem toxicity. The median blood zolpidem concentration was 0.20 mg/L (range 0.05–3.50 mg/L), with no significant gender difference. Drug toxicity cases involving zolpidem had significantly higher median blood zolpidem concentrations than other cases (0.50 vs. 0.10 mg/L). In 83.5% of cases, psychoactive substances other than zolpidem were detected, most commonly antidepressants (46.2%), benzodiazepines (35.2%), opioids (26.4%), and alcohol (39.6%). In summary, zolpidem was a factor contributing to death in a large proportion of cases, predominately involving drug toxicity and suicide.     

Analytical Challenge in Postmortem Toxicology Applied to a Human Body Found into a Lake after Three Years Immersion

The body of a 30‐year‐old woman was found in Como lake at a depth of about 120 meters in her own car after 3 years of immersion. The aim of this study was to evaluate psychoactive drugs as well as alcohol biomarkers in biological matrices. The following analyses were initially performed: GC‐MS systematic toxicological analysis on biological fluids and tissues; GC‐MS analysis of drugs of abuse on pubic hair; direct ethanol metabolite determination in pubic hair by LC‐MS/MS. After 7 years, the samples, that had been stored at ?20°C, were re‐analyzed and submitted to an LC‐MS/MS targeted screening method, using multiple reaction monitoring mode. These analyses detected citalopram (150–3000 ng/mL), desmethylcitalopram (50–2300 ng/mL), clotiapine (20–65 ng/mL), and ethyl glucuronide (97 pg/mg). The methods showed an acceptable reproducibility, and the concentrations of citalopram and desmethylcitalopram calculated through the two analytical techniques did not significantly differ in biological fluids.     

合成大麻素类新精神活性物质4F-MDMB-BICA的检测

目的 建立基于红外光谱(fourier transform infrared,FT-IR)、气相色谱-质谱联用(gas chromatography-mass spectrometry,GC-MS)、高分辩质谱(high resolution mass spectrometer,HRMS)和核磁共振波谱(nuclear...     

Toxicology and circumstances of death of homicide victims in New South Wales, Australia 1996-2005.

To determine the prevalence and circumstances of psychoactive substances amongst homicide victims, 485 consecutive cases autopsied at the NSW Department of Forensic Medicine (1/1/1996-12/31/2005) were analyzed. Substances were detected in 62.6% of cases, and illicit drugs in 32.8%. Alcohol, cannabis, opioids, and psychostimulants were most commonly detected. Alcohol and cannabis were both more prevalent amongst males. Mean ages were significantly younger for decedents who tested positive for a substance and for an illicit drug. Cases where death resulted from a physical altercation were more likely to have had alcohol and cannabis present. Illicit drugs were prominent amongst firearms deaths. The proportion of alcohol positive cases increased from 25.0% on Monday to 49.4% for Saturdays/Sundays. Alcohol was more common in incidents in the 0001-0600 h and 1800-2400 h periods. Psychoactive substances appear to substantially increase the risk of homicide, although there are important differences between drug classes in the circumstances of such incidents.