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The invisible crisis facing forensic providers in the United States 美国法医服务提供者面临的无形危机
Q1 Social Sciences Pub Date : 2025-08-06 DOI: 10.1016/j.fsisyn.2025.100631
There is a dissonance between the public perception of forensic practice in the United States and reality. Portrayed as infallible and universally available, the truth is that the awkward evolution of forensic practice has created fissures in its foundations, affecting both the quality and quantity of these critical services. These fissures have only widened over time, creating problems that require creative solutions.
Within the United States, every level of government provides forensic services, and there is no overarching authority over forensic providers. The recent reevaluation of the Chevron deference doctrine by the Supreme Court ensures that this is unlikely to change in the foreseeable future. Under Chevron deference, courts would defer to regulatory agencies interpretations when laws were ambiguous. This new ruling transfers that responsibility back to the courts, making the creation of a new regulatory agency over forensic providers even less likely. Thus, any meaningful change to forensic practice must come from within the profession. As unlikely as this may seem, it has occurred before.
This perspective allows us to see the hidden challenges forensic providers face and propose potential solutions that practitioners can implement to increase the quality of their work and the resilience of the system they operate within. By evaluating how forensic practice has implemented change in the past, this paper proposes solutions that have worked before and expands on others from different industries with similar challenges.
在美国,公众对法医实践的认知与现实之间存在着不协调。被描绘成绝对可靠和普遍可用的事实是,法医实践的尴尬演变在其基础上造成了裂缝,影响了这些关键服务的质量和数量。随着时间的推移,这些裂痕只会扩大,产生需要创造性解决方案的问题。在美国,各级政府都提供法医服务,对法医提供者没有最高权威。最近最高法院对雪佛龙服从原则的重新评估,确保了这一点在可预见的未来不太可能改变。根据雪佛龙的说法,当法律模棱两可时,法院将服从监管机构的解释。这项新的裁决将责任转移回法院,使得建立一个新的监管机构来监管法医提供者的可能性更小。因此,对法医实践的任何有意义的改变都必须来自专业内部。尽管这看起来不太可能,但以前就发生过。这一视角使我们能够看到司法鉴定提供者面临的潜在挑战,并提出从业者可以实施的潜在解决方案,以提高他们的工作质量和他们所处系统的弹性。通过评估取证实践在过去是如何实施变革的,本文提出了以前有效的解决方案,并扩展到其他面临类似挑战的不同行业。
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引用次数: 0
Fast DNA reports for investigative leads in casework practice: An automated workflow for mixture analysis using database searching based on probabilistic genotyping 快速DNA报告的调查线索在案件工作实践:一个自动化的工作流程,混合分析使用数据库搜索基于概率基因分型
Q1 Social Sciences Pub Date : 2025-08-06 DOI: 10.1016/j.fsisyn.2025.100632
Corina C.G. Benschop, Martin Slagter, Laurens J.W. Grol, Pauline Hovers, Jord H.A. Nagel, Sophie Smit, Francisca E. Duijs, Alexander L.J. Kneppers
The Fast DNA Identification Line (Fast ID Line) is a series of software solutions automating the process of DNA profile analysis, contamination checks, comparison with reference profiles, elimination and criminal DNA database comparison, report generation and dissemination of results to law enforcement. The Fast ID Line v1.0 focussed on identifying candidates that could be contributors to single-source profiles or major contributors to mixed DNA profiles.
In this paper, the Fast ID Line was extended to automatically report on mixture profiles with up to four contributors. This software, v2.0, includes extended profile analysis rules, a machine learning model for number of contributors estimation and a probabilistic genotyping model for database searching. Suitability criteria were established for the automatically analysed DNA profiles and reporting of the results.
End-to-end testing using casework data demonstrated that the Fast ID Line v2.0: 1) delivered >80 % of DNA reports within three working days, 2) retrieved 1.9-fold more candidates compared to v1.0 (304 vs 162/777 database searches), and 3) reported 72 % of candidates that were reported in the manual casework workflow.
Police and public prosecution across the Netherlands now make use of the Fast ID Line reports with investigative leads. The automated reports are quickly available, allowing law enforcement to act on DNA findings for intelligence purposes before receiving the expert report. Additional information was provided in only 33% of the expert reports. This indicates that, in the majority of cases, the Fast ID Line results only require a confirmation check by a DNA expert, saving valuable time.
快速DNA识别线(Fast ID Line)是一系列软件解决方案,可自动完成DNA图谱分析、污染检查、与参考图谱比较、消除和刑事DNA数据库比较、报告生成和向执法部门发布结果等过程。Fast ID Line v1.0专注于识别可能是单一来源谱的贡献者或混合DNA谱的主要贡献者的候选对象。在本文中,快速ID线被扩展到自动报告最多有四个贡献者的混合概要文件。该软件,v2.0,包括扩展的配置文件分析规则,用于贡献者数量估计的机器学习模型和用于数据库搜索的概率基因分型模型。建立了自动分析DNA图谱和报告结果的适用性标准。使用案例工作数据的端到端测试表明,Fast ID Line 2.0版本:1)在三个工作日内提供了80%的DNA报告,2)与1.0版本相比,检索到的候选对象增加了1.9倍(304对162/777数据库搜索),3)报告了在手动案例工作流程中报告的72%的候选对象。现在,荷兰各地的警方和公诉部门都在使用快速身份识别热线(Fast ID Line)提供的调查线索。自动报告可以快速获得,允许执法部门在收到专家报告之前根据DNA发现采取情报行动。只有33%的专家报告提供了补充资料。这表明,在大多数情况下,快速ID线的结果只需要DNA专家的确认检查,节省了宝贵的时间。
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引用次数: 0
Drone forensics redefined: Integrating live, digital, and non-digital evidence acquisition systems 无人机取证重新定义:集成实时、数字和非数字证据采集系统
Q1 Social Sciences Pub Date : 2025-08-06 DOI: 10.1016/j.fsisyn.2025.100635
Dongkyu Lee , Wook Kang
The rapid development and proliferation of drone technology have led to an increase in various threats. In particular, the number of attacks, crimes, and accidents using drones is continuously expanding, and the need for a systematic response is growing. Existing response strategies have mainly focused on real-time defense-oriented technologies and policies, such as detection, identification, and neutralization of drones. However, recently, the importance of drone forensics, which identifies the flight path of drones, pilot information, and the cause of accidents after an incident, has been highlighted. Drone forensics combines elements of traditional digital forensics and non-digital (physical) forensics, and live forensics technology that collects and analyzes data immediately after an incident plays a crucial role. Drone forensics has distinct technical characteristics compared to general forensics, and this study presents a systematic analysis framework and analysis algorithm structure that reflects these technical characteristics and convergent analysis factors. It comprehensively reviews the major drone forensics technologies currently being utilized. This will help to secure the legal evidence capability of drone forensics and increase its usefulness as evidence.
无人机技术的快速发展和扩散导致了各种威胁的增加。特别是,利用无人机的攻击、犯罪、事故不断增加,需要系统应对。现有的应对策略主要集中在实时防御技术和政策上,如无人机的检测、识别和中和。但最近,在事故发生后,查明无人机飞行路线、驾驶员信息、事故原因的无人机取证的重要性得到了强调。无人机取证结合了传统数字取证和非数字(物理)取证的元素,现场取证技术在事件发生后立即收集和分析数据,发挥着至关重要的作用。与一般取证相比,无人机取证具有明显的技术特征,本研究提出了反映这些技术特征和收敛分析因素的系统分析框架和分析算法结构。它全面回顾了目前正在使用的主要无人机取证技术。这将有助于确保无人机取证的法律证据能力,提高其作为证据的实用性。
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引用次数: 0
The problem with eliminations: Why forensic comparisons need false negative rates 消除的问题:为什么法医比较需要假阴性率
Q1 Social Sciences Pub Date : 2025-07-31 DOI: 10.1016/j.fsisyn.2025.100621
Maria Cuellar
This article examines the overlooked risk of false negative errors arising from eliminations in forensic firearm comparisons. While recent reforms in forensic science have focused on reducing false positives, eliminations — often based on class characteristics or intuitive judgments — receive little empirical scrutiny despite their potential to exclude true sources. In cases involving a closed pool of suspects, eliminations can function as de facto identifications, introducing serious risk of error. A review of existing validity studies reveals that many report only false positive rates, failing to provide a complete assessment of method accuracy. This asymmetry is reinforced by professional guidelines, such as those from AFTE, and echoed in major government reports, including those from NAS and PCAST. The article argues that eliminations, like identifications, must be validated through rigorous testing and reported with transparent error rates. It further cautions against the use of “common sense” eliminations in the absence of empirical support and highlights the dangers of contextual bias when examiners are aware of investigative constraints. Five policy recommendations are proposed to improve the scientific treatment and legal interpretation of eliminations, including balanced reporting of false positive and false negative rates, validation of intuitive judgments, and clear warnings against using eliminations to infer guilt in closed-pool scenarios. Without reform, eliminations will continue to escape scrutiny, perpetuating unmeasured error and undermining the integrity of forensic conclusions.
这篇文章检查了被忽视的风险假阴性错误产生的消除在法医枪支比较。虽然法医学最近的改革侧重于减少误报,但排除——通常基于阶级特征或直觉判断——尽管有可能排除真实来源,却很少受到实证审查。在涉及一个封闭的嫌疑犯池的案件中,排除可能起到事实上的识别作用,造成严重的错误风险。对现有有效性研究的回顾表明,许多报告只报告假阳性率,未能提供方法准确性的完整评估。这种不对称被专业指南(如来自AFTE的指南)所强化,并在包括NAS和PCAST在内的主要政府报告中得到呼应。这篇文章认为,消除和识别一样,必须通过严格的测试来验证,并以透明的错误率报告。它进一步警告说,在缺乏经验支持的情况下,不要使用“常识”排除,并强调了当审查员意识到调查限制时,背景偏见的危险。提出了五项政策建议,以提高对排除的科学处理和法律解释,包括平衡报告假阳性和假阴性率,验证直觉判断,明确警告不要在封闭池场景中使用排除来推断有罪。不进行改革,淘汰将继续逃避审查,使无法衡量的错误永久化,并破坏法医结论的完整性。
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引用次数: 0
Forensic biobank; towards comprehensive forensic genetic frequency database for the Kenyan population 法医生物;建立肯尼亚人口的综合法医遗传频率数据库
Q1 Social Sciences Pub Date : 2025-07-29 DOI: 10.1016/j.fsisyn.2025.100633
Eva K. Aluvaala Nambati , Edward Muge , Belinda Azzam , Diana Maritim , Ngure Kirosh , Luna Kamau , Solomon Mpoke , Winfrida Cheriro , Lewis Karani , Martin Sang , Abdiaziz Gosar , Olipher Makwaga , Lydia Eyase , Herzel Tiffany Wandera , Sharon Ariga , James Nyabera , Milka Mwangi , Francis Kimani , Wallace Bulimo
Forensic genetic frequency databases (FGFD) are used in estimating the probability of a DNA match in forensic investigations. They provide reference population data that can be used for statistical estimation for the rarity of a genotype, haplotype or a DNA profile in a population hence giving probative value for forensic evidence.
Currently, three FGFD databases are recommended by the International Society for Forensic Genetics (ISFG) for forensic use; the Y-Chromosome Haplotype Reference Database (YHRD), the EDNAP Mitochondrial DNA Population Database (EMPOP), and the STRs for Identity ENFSI Reference Database (STRidER).
There is need to generate updated and comprehensive genetic frequency data for the Kenyan population in compliance with ethical standards.
This study sought to develop a forensic biobank to facilitate generation of comprehensive genetic frequency data for the Kenyan population. A total of 893 samples were collected from study volunteers in compliance with prescribed ethical standards. The data set comprises 60.8 % Bantu, 24.9 % Nilotic, and 14.3 % Cushitic samples closely mirroring current population structure in Kenya. The samples are currently stored in duplicate as FTA cards and extracted DNA.
132 quality mitogenome reference data has been generated for the coastal region in Kenya. With the broad consent obtained, the resource will be used to generate additional mitogenome reference data for other geographical regions, Y-chromosome haplotype and autosomal STRs for inclusion in recommended forensic databases as per revised guidelines. With the emergence of new technologies in forensic genetics, we anticipate the resource will be valuable in forensic genetics validation studies in future.
法医遗传频率数据库(FGFD)在法医调查中用于估计DNA匹配的概率。它们提供参考种群数据,可用于统计估计种群中基因型、单倍型或DNA谱的稀有性,从而为法医证据提供证明价值。目前,国际法医遗传学学会(ISFG)推荐三个FGFD数据库供法医使用;y染色体单倍型参考数据库(YHRD)、EDNAP线粒体DNA种群数据库(EMPOP)和STRs for Identity ENFSI参考数据库(STRidER)。有必要根据伦理标准为肯尼亚人口生成最新和全面的遗传频率数据。本研究旨在开发一个法医生物库,以促进肯尼亚人口全面遗传频率数据的生成。按照规定的道德标准,从研究志愿者中收集了总共893个样本。该数据集包括60.8%的班图人,24.9%的尼罗河人和14.3%的库希特人样本,密切反映了肯尼亚当前的人口结构。目前,这些样本一式两份存储为FTA卡,并提取dna。肯尼亚沿海地区已生成132个高质量的有丝分裂基因组参考数据。在获得广泛同意的情况下,该资源将用于生成其他地理区域、y染色体单倍型和常染色体str的额外有丝分裂基因组参考数据,以便根据修订后的指南纳入推荐的法医数据库。随着法医遗传学新技术的出现,我们预计这些资源将在未来的法医遗传学验证研究中发挥重要作用。
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引用次数: 0
Quantifying the strength of palmprint comparisons: Majority identifications with surprisingly low value 量化掌纹比较的强度:大多数识别值低得惊人
Q1 Social Sciences Pub Date : 2025-07-23 DOI: 10.1016/j.fsisyn.2025.100628
Meredith Coon , Thomas Busey
Friction ridge examiners report conclusions to palm impression comparisons similarly to fingerprint impression comparisons, although several key differences exist. These include an extensive search process in palm impressions, differences in minutiae rarity, and orientation challenges that most fingerprint comparisons do not require. Most US laboratories use a three-conclusion scale that includes Identification, Exclusion, and Inconclusive, which have not been calibrated against the actual strength of the evidence in palmprint comparisons. To measure the strength of the evidence of palmprint impressions, the present work constructs likelihood ratios using an ordered probit model based on distributions of examiner responses in an error rate study. Many likelihood ratios calculated are quite modest and the current articulation scales may overestimate the strength of support for same source propositions by up to five orders of magnitude. These likelihood ratios help calibrate the articulation language and may offer an alternative to categorical reporting scales.
摩擦脊审查员对手掌印痕比较的报告结论与指纹印痕比较相似,尽管存在几个关键差异。这些包括手掌印的广泛搜索过程,细微稀有度的差异,以及大多数指纹比较不需要的方向挑战。大多数美国实验室使用三结论量表,包括识别、排除和不确定,这些量表没有根据掌纹比较中证据的实际强度进行校准。为了测量掌印证据的强度,本研究使用基于错误率研究中考官反应分布的有序概率模型构建了似然比。许多计算出的似然比是相当适度的,而目前的表达量表可能会高估对同一来源命题的支持强度,最高可达五个数量级。这些似然比有助于校准发音语言,并可能提供分类报告量表的替代方案。
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引用次数: 0
Transparent reporting in forensic Science: Exploring its meaning and challenges 司法科学中的透明报告:探索其意义和挑战
Q1 Social Sciences Pub Date : 2025-07-18 DOI: 10.1016/j.fsisyn.2025.100630
Kristy A. Martire
The forensic and scientific communities widely endorse transparency as a core principle and fundamental obligation of forensic science reporting. Yet the definition of transparency - ironically – remains opaque. This ambiguity impacts scientist's ability to fulfill their obligations when reporting forensic findings to justice systems as the primary consumer. Applying Elliott's 2022 taxonomy of transparency clarifies the issue, revealing that transparency is central to achieving Reliability, Assessment, Justice, Accountability and Innovation goals. It involves disclosing information about the scientists' Authority, Compliance, Basis, Justification, Validity, Disagreements, and Context, and shows that the audiences for these disclosures includes not only primary consumers, but also a range of agents, actors, and stakeholders. This complexity creates a multidimensional challenge for scientists and forensic science service providers, requiring a careful balance between competing demands. Templates can mitigate some of these challenges, but must be coupled with ongoing collaboration among forensic scientists, legal stakeholders, and institutional bodies to ensure that reporting practices evolve in line with professional obligations, scientific rigor and the realities of forensic practice.
法医学和科学界普遍认同透明度是法医学报告的核心原则和基本义务。然而,具有讽刺意味的是,透明度的定义仍然不透明。这种模糊性影响了科学家作为主要消费者向司法系统报告法医发现时履行义务的能力。运用艾略特的2022透明度分类法澄清了这个问题,揭示了透明度是实现可靠性、评估、公正、问责制和创新目标的核心。它涉及披露有关科学家的权威、遵从性、依据、论证、有效性、分歧和背景的信息,并表明这些披露的受众不仅包括主要消费者,还包括一系列代理人、行动者和利益相关者。这种复杂性给科学家和法医科学服务提供者带来了多方面的挑战,需要在相互竞争的需求之间取得谨慎的平衡。模板可以减轻其中的一些挑战,但必须与法医科学家、法律利益相关者和机构机构之间的持续合作相结合,以确保报告实践与专业义务、科学严谨性和法医实践的现实相一致。
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引用次数: 0
Validation of the EuroForMix at the Brazilian Federal Police: Analysis of matches involving complex genetic profiles 巴西联邦警察对EuroForMix的验证:涉及复杂基因图谱的匹配分析
Q1 Social Sciences Pub Date : 2025-07-18 DOI: 10.1016/j.fsisyn.2025.100619
Ananda Duarte , Augusto Soares Leite Ribeiro , Marlon Anselmo Duarte da Costa , Renato Teodoro Fereira de Paranaíba , Apoena de Oliveira Lopes , Luiz Guilherme Barros Cocentino , Bruno Rodrigues Trindade , Carlos Eduardo Martinez de Medeiros , Cristina Moniz de Aragão Gualda , Aline Costa Minervino
DNA mixture profiles and single profiles with drop-out originate from complex biological samples, whose interpretation poses challenges such as determining the number of contributors and evaluating the weight of genetic evidence. At the laboratory of the Forensic Genetics Service of the Federal Police (SEPGEF), the analysis of complex genetic profiles is performed using the LRmix Studio™ software, which has been discontinued. Thus, members of the National DNA Database (BNPG) and SEPGEF conducted this study to validate the use of the EuroForMix software in evaluating matches of complex genetic profiles in Federal Police cases. Simulated mixture profiles of two heterozygous individuals in 22 of the 23 autosomal genetic markers examined were analyzed. The mixtures, amplified in triplicate, were made in proportions of 1:1, 1:2, 1:4, and 1:6, with one-third of the samples subjected to degradation by ultraviolet (UV) radiation for 10 min, one-third for 20 min, and one-third without UV degradation. The LRmix Studio™ and EuroForMix were used to quantify the weight of genetic evidence observed in matches with the reference profiles used in the simulated samples. The analysis involved three situations: 1. Evaluation of the likelihood ratio (LR) between a DNA profile with drop-out classified as one contributor compared to a reference profile; 2. Evaluation of the LR between a mixture profile classified as having two contributors compared to a reference profile (major); 3. Evaluation of the LR between a mixture profile classified as having two contributors conditioning on one contributor (minor). Additionally, situations 2 and 3 were assessed in modified forms: the evaluation of the LR between a two-person mixture profile and a reference profile (minor); and the evaluation of the LR for a two-person mixture profile conditioned on the major contributor. Finally, six real cases, previously reported by the laboratory using LRmix Studio™, were analyzed with EuroForMix. The values obtained in both software were compared. The results showed that EuroForMix generally presented higher LR values than LRmix Studio™. Therefore, the EuroForMix software was validated for routine use at SEPGEF in the three situations mentioned.
DNA混合图谱和有缺失的单一图谱来自复杂的生物样本,其解释带来了诸如确定贡献者数量和评估遗传证据权重等挑战。在联邦警察法医遗传学服务(SEPGEF)实验室,使用LRmix Studio™软件对复杂的基因图谱进行分析,该软件已停产。因此,国家DNA数据库(BNPG)和SEPGEF的成员进行了这项研究,以验证EuroForMix软件在联邦警察案件中评估复杂基因图谱匹配的使用。分析了23个常染色体遗传标记中的22个中两个杂合个体的模拟混合谱。将混合物放大三份,按1:1、1:2、1:4和1:6的比例配制,其中三分之一的样品接受紫外线(UV)辐射降解10分钟,三分之一接受20分钟,三分之一不进行紫外线降解。使用LRmix Studio™和EuroForMix来量化与模拟样品中使用的参考谱相匹配的遗传证据的权重。分析涉及三种情况:1。与参考DNA谱相比,将辍学分类为一个贡献者的DNA谱之间的似然比(LR)进行评估;2. 与参考剖面(主要)相比,评估具有两个贡献者的混合剖面之间的LR;3. 对被分类为具有两个贡献者的混合剖面之间的LR进行评估,以一个贡献者为条件(次要)。此外,对情况2和3进行了修改形式的评估:评估两人混合剖面和参考剖面(次要)之间的LR;以及以主要贡献者为条件的双人混合轮廓的LR评估。最后,使用EuroForMix分析之前由实验室使用LRmix Studio™报告的6例真实病例。比较两种软件的结果。结果表明,EuroForMix的LR值普遍高于LRmix Studio™。因此,在上述三种情况下,EuroForMix软件在SEPGEF上进行了常规使用验证。
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引用次数: 0
Errors in toxicology testing and the need for full discovery 毒理学测试中的错误和全面发现的必要性
Q1 Social Sciences Pub Date : 2025-07-17 DOI: 10.1016/j.fsisyn.2025.100629
Aaron Olson , Charles Ramsay
Despite toxicology's foundation in analytical chemistry and quantitative measurements, it remains vulnerable to errors that can impact criminal justice outcomes. This paper presents a review of notable errors in toxicology collected over a combined 48 years of field experience. We highlight cases of toxicology errors from across multiple jurisdictions, categorizing them by type: traceability errors, calibration errors, discovery violations, maintenance failures, source code defects, fraud, errors due to interfering substances, reporting errors, laboratory contamination, and chain of custody breaches.
Our analysis reveals that many errors persisted for years before detection, with some lasting over a decade. Discovery often came from external sources rather than internal quality controls. Errors ranged from technical failures to deliberate misconduct, affecting thousands of cases. Notable patterns include institutional resistance to disclosure, retaliation against whistleblowers, and systematic withholding of exculpatory evidence. The compilation demonstrates vulnerabilities in toxicology. Key reforms needed include transparency through online discovery portals, mandatory retention of digital data, independent laboratory accreditation, whistleblower protections, and regular third-party audits. By examining past errors, the forensic science community can develop policies to prevent similar mistakes and enhance both scientific integrity and the pursuit of justice.
尽管毒理学的基础是分析化学和定量测量,但它仍然容易受到可能影响刑事司法结果的错误的影响。本文提出了一个值得注意的错误,在毒理学收集超过48年的现场经验的审查。我们重点介绍了来自多个司法管辖区的毒理学错误案例,并按类型对其进行了分类:可追溯性错误、校准错误、发现违规、维护故障、源代码缺陷、欺诈、干扰物质导致的错误、报告错误、实验室污染和监管链违规。我们的分析显示,许多错误在被发现前持续了数年,有些甚至持续了10多年。发现往往来自外部来源,而不是内部质量控制。错误包括从技术故障到故意不当行为,影响了数千起案件。值得注意的模式包括对披露的制度性抵制,对举报人的报复,以及系统性地隐瞒无罪证据。该汇编显示了毒理学的脆弱性。需要进行的关键改革包括通过在线发现门户实现透明度、强制保留数字数据、独立实验室认证、举报人保护和定期第三方审计。通过审查过去的错误,法医科学界可以制定政策来防止类似的错误,并加强科学的完整性和对正义的追求。
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引用次数: 0
Metabolic patterns of new psychoactive substances: Methyl-ketamine and 2-oxo-PCE in rats using UHPLC-QTOF analysis 新型精神活性物质的代谢模式:甲基氯胺酮和2-氧- pce在大鼠体内的UHPLC-QTOF分析
Q1 Social Sciences Pub Date : 2025-07-14 DOI: 10.1016/j.fsisyn.2025.100623
Yu-gang Cai , Yan-jun Wang , Yong-fu Wu , Jia-yi Feng , Yan Mo , Qing-hong Wang , Yong Dai
This study investigated the metabolic profiles of two isomeric psychoactive agents, methyl-ketamine [2-(ortho-tolyl)-2-(methylamino)cyclohexanone] and 2-oxo-PCE [2-(phenyl)-2-(ethylamino)cyclohexanone], in rats. Following oral administration, blood, liver, and urine samples were collected at timed intervals and analyzed via ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Metabolomic comparisons revealed distinct metabolic pathways driven by structural differences. Methyl-ketamine primarily underwent cyclohexanone hydroxylation, dehydration, N-demethylation, cyclohexanone carbonyl hydrogenation, and glucuronidation, with N-dealkylation as the dominant process. In contrast, 2-oxo-PCE metabolism involved carbonyl hydrogenation of cyclohexanone, N-diethylation, deamination, hydroxylation, dehydration, and glucuronidation. Structural variations—specifically the steric hindrance imposed by the methyl group on o-tolyl in methyl-ketamine—were identified as key factors influencing metabolic divergence. This hindered the carbonyl hydrogenation of cyclohexanone observed in 2-oxo-PCE, while promoting hydroxylation/dehydration reactions in methyl-ketamine. Post-N-dealkylation, methyl-ketamine retained cyclohexyl hydroxylation/dehydration, whereas 2-oxo-PCE exhibited deamination and cyclohexanone carbonyl hydrogenation/dehydration. Notably, urinary metabolite profiles in humans were mirrored those in rats, and relevance was shown. It was elucidated how structural isomerism dictating metabolic outcomes and offering insights into the mechanistic basis of new psychoactive substances. The study underscored steric effects as critical determinants of metabolic pathways and provided a foundation for predicting pharmacokinetic behavior in related compounds.
本研究研究了两种异构体精神活性药物甲基氯胺酮[2-(邻苯二甲酸)-2-(甲氨基)环己酮]和2-氧- pce[2-(苯基)-2-(乙胺)环己酮]在大鼠体内的代谢谱。口服给药后,每隔一段时间采集血液、肝脏和尿液样本,并通过超高高效液相色谱-四极杆飞行时间质谱(UHPLC-QTOF-MS)进行分析。代谢组学比较揭示了由结构差异驱动的不同代谢途径。甲基氯胺酮主要经过环己酮羟基化、脱水、n -去甲基化、环己酮羰基加氢和葡萄糖醛酸化,其中n -脱烷基为主要过程。相反,2-氧- pce代谢包括环己酮羰基加氢、n -二乙基化、脱胺、羟基化、脱水和葡萄糖醛酸化。结构差异——特别是甲基对甲基氯胺酮中的邻甲基基施加的位阻——被认为是影响代谢差异的关键因素。这阻碍了环己酮在2-氧基pce中的羰基加氢反应,而促进了甲基氯胺酮的羟基化/脱水反应。n -脱烷基后,甲基氯胺酮保持环己基羟基化/脱水,而2-氧- pce则表现出脱胺和环己酮羰基氢化/脱水。值得注意的是,人类的尿液代谢物谱与大鼠的相似,并显示出相关性。阐明了结构异构体如何决定代谢结果,并为新的精神活性物质的机制基础提供了见解。该研究强调了立体效应作为代谢途径的关键决定因素,并为预测相关化合物的药代动力学行为提供了基础。
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引用次数: 0
期刊
Forensic Science International: Synergy
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