Ayman Alzu'bi, Ejlal Abu-El-Rub, Fatimah A Almahasneh, Rawan Almazari, Amani Kasasbeh, Heba F Ai-Jariri, Amneh Alrabie, Raed M Al-Zoubi
{"title":"Synthetic Cannabinoid AB-FUBINACA Negatively Impacted the Male Fertility and Induced Testicular Toxicity.","authors":"Ayman Alzu'bi, Ejlal Abu-El-Rub, Fatimah A Almahasneh, Rawan Almazari, Amani Kasasbeh, Heba F Ai-Jariri, Amneh Alrabie, Raed M Al-Zoubi","doi":"10.1007/s11419-025-00739-y","DOIUrl":"https://doi.org/10.1007/s11419-025-00739-y","url":null,"abstract":"<p><strong>Purpose: </strong>The recreational use of synthetic cannabinoids (SCs) by adolescents and adults has markedly increased in recent years. Previous studies demonstrated that exposure to SCs is associated with multiple adverse health effects. Nevertheless, little is known about the effects of these substances on male fertility. The current study aimed to investigate the toxicological effects of subacute exposure to synthetic cannabinoid AB-FUBINACA on male reproductive system in mice.</p><p><strong>Methods: </strong>Adult male Balb/c mice received daily intraperitoneal injections of various doses of AB-FUBINACA (0.75, 1.5, and 3 mg/kg for 3 weeks). Using biochemical and molecular methodologies, the impact of AB-FUBINACA on serum levels of reproductive hormones, sperm viability as well as various parameters in testicular tissue were evaluated.</p><p><strong>Results: </strong>Our findings demonstrated that AB-FUBINACA induces dose-dependent reduction in testosterone levels in the serum, but not in follicle-stimulating hormone or luteinizing hormone. AB-FUBINACA treatment also causes a significant dose related decrease in sperm viability. These findings were associated with higher level of oxidative stress (GP91 expression and malondialdehyde level) and elevated expression of key regulators of apoptosis (Bax and caspase-3) as well as reduced expression of mitochondrial respiratory chain complexes SDHB (II), UQCRC2 (III), and ATP5a (V) in the testicular tissue.</p><p><strong>Conclusion: </strong>From these findings, it can be concluded that exposure to AB-FUBINACA can interfere with the normal physiology and functioning of the male reproductive organs. Hence, gaining insight into the mechanisms by which SCs interfere with male fertility could guide future interventions and treatments.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of blood impurity removal efficiency using the QuEChERS method.","authors":"Haruki Kuze, Haruhi Yoshida, Hikaru Tamagawa, Taichi Nishihori, Yuri Tokugawa, Fumika Yamamoto, Hiroshi Matsumoto, Kazuo Harada","doi":"10.1007/s11419-025-00740-5","DOIUrl":"https://doi.org/10.1007/s11419-025-00740-5","url":null,"abstract":"<p><strong>Purpose: </strong>Comparison of the impurity removal efficiencies of the deproteinization and Quick, Easy, Cheap, Effective, Rugged, Safe (QuEChERS) methods, which are pretreatment methods for drug analysis adopted by many forensic autopsy institutions, was performed.</p><p><strong>Method: </strong>Residual cardiac blood samples were pretreated using deproteinization and QuEChERS methods. The residual amounts of total proteins, total lipids, glucose, galactose, electrolytes, and inorganic elements were measured. We also compared the recovery rates and matrix factors when using liquid chromatography/tandem mass spectrometry (LC/MS/MS).</p><p><strong>Results: </strong>The residual rates of total proteins, total lipids, glucose, galactose, and electrolytes using the deproteinization method were 16%, 75%, 75%, 90%, and 91%, respectively. In contrast, the QuEChERS method showed 1.1%, 11%, 7.6%, 9.4%, and 20%, respectively. The amounts of Mg and Mn in QuEChERS increased compared with those before treatment, but other inorganic elements remained at 9.6-89% during deproteinization and 0.30-17% in the QuEChERS. The recovery rate of metformin was low in QuEChERS; however, no differences were observed in the recovery rates or matrix factors of the other 16 drugs between deproteinization and QuEChERS.</p><p><strong>Conclusions: </strong>This study quantitatively demonstrated that QuEChERS is extremely efficient at removing impurities from blood compared with deproteinization methods. QuEChERS has poor recovery rates for highly polar drugs but does not prevent their detection. The QuEChERS method is superior to the deproteinization method, considering the load of impurities on the analytical instruments.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meejung Park, Sungmin Moon, Nahyun Lee, Jihyun Kim
{"title":"Simultaneous quantitative determination of 2-fluoro-2-oxo-phenylcyclohexylethylamine, methylenedioxymethamphetamine and ketamine in postmortem blood using liquid chromatography-tandem mass spectrometry.","authors":"Meejung Park, Sungmin Moon, Nahyun Lee, Jihyun Kim","doi":"10.1007/s11419-025-00743-2","DOIUrl":"https://doi.org/10.1007/s11419-025-00743-2","url":null,"abstract":"<p><strong>Purpose: </strong>The abuse of 2-fluoro-2-oxo-phenylcyclohexylethylamine (2F-2-oxo-PCE), a dissociative anesthetic structurally related to phencyclidine (PCP) and ketamine, has recently increased in South Korea. This study presented the first forensic toxicological detection of 2F-2-oxo-PCE in autopsy cases and described a validated method for the simultaneous quantification of 2F-2-oxo-PCE, methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), ketamine, and norketamine in postmortem blood.</p><p><strong>Method: </strong>2F-2-oxo-PCE and its metabolite, 2F-deschloronorketamine (2F-DCNK) were identified using gas chromatography-mass spectrometry (GC-MS). A liquid chromatography-tandem mass spectrometry (LC-MS/MS) with solid-phase extraction (SPE) was developed and validated for the simultaneous quantification of 2F-2-oxo-PCE, MDMA, MDA, ketamine and norketamine in blood.</p><p><strong>Results: </strong>The validation parameters including linearity, accuracy, precision, matrix effect, and recovery were satisfactory. In postmortem blood samples, 2F-2-oxo-PCE concentrations ranged from 664 to 7911 ng/mL. Concurrent detection with MDMA and ketamine suggested possible polydrug use contributing to fatal outcomes.</p><p><strong>Conclusions: </strong>The validated LC-MS/MS method is suitable for forensic applications and may enhance the toxicological profiling of emerging dissociative substances. The results can provide critical baseline data for interpreting 2F-2-oxo-PCE-related intoxications.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a novel isolation method for Δ<sup>9</sup>-tetrahydrocannabinolic acid-A from cannabis suitable for forensic laboratories.","authors":"Kenji Tsujikawa, Yuki Okada, Tadashi Yamamuro, Kenji Kuwayama, Tatsuyuki Kanamori, Yuko T Iwata","doi":"10.1007/s11419-025-00742-3","DOIUrl":"https://doi.org/10.1007/s11419-025-00742-3","url":null,"abstract":"<p><strong>Purpose: </strong>Δ<sup>9</sup>-Tetrahydrocannabinolic acid-A (Δ<sup>9</sup>-THCA-A) is a precursor of Δ<sup>9</sup>-tetrahydrocannabinol in cannabis. Here, considering applicability to ordinary forensic laboratories, we developed a novel isolation method for Δ<sup>9</sup>-THCA-A without the need for special equipment.</p><p><strong>Methods: </strong>Dried pulverized cannabis inflorescence (2 g) was extracted with acetonitrile. After the extract was treated with graphite carbon powder to remove chlorophyll, the solvent was replaced with methanol. The methanol solution was diluted with aqueous sodium hydroxide solution and then washed with a mixture of n-hexane/ethyl acetate (7:1, v/v). The remaining aqueous layer was acidified with acetic acid and extracted with the n-hexane/ethyl acetate mixture. The extract was purified by silver nitrate-impregnated silica gel column chromatography.</p><p><strong>Results: </strong>The isolation procedure gave a pale beige solid as the final product. The final product was identified as Δ<sup>9</sup>-THCA-A by comparison of the analytical results of gas chromatography/mass spectrometry (GC/MS) after trimethylsilylation and high-performance liquid chromatography with ultraviolet detection (HPLC-UV) with an authentic standard. The final product was confirmed to be highly pure by <sup>1</sup>H-nuclear magnetic resonance spectroscopy in addition to GC/MS and HPLC-UV.</p><p><strong>Conclusions: </strong>This novel isolation method gave highly pure Δ<sup>9</sup>-THCA-A without using special purification equipment, such as a flash chromatography system or an HPLC system with a fraction collector, which are uncommon in forensic laboratories. This method will be useful for many forensic laboratories that find it difficult to obtain commercial Δ<sup>9</sup>-THCA-A as a standard.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N Arbouche, A Geraut, F Kientzy, J S Raul, P Kintz
{"title":"A deadly root and the science behind it: LC-HRMS and LC-MS/MS analysis in an aconite-induced suicide.","authors":"N Arbouche, A Geraut, F Kientzy, J S Raul, P Kintz","doi":"10.1007/s11419-025-00741-4","DOIUrl":"https://doi.org/10.1007/s11419-025-00741-4","url":null,"abstract":"<p><strong>Purpose: </strong>Aconitine is a highly toxic alkaloid found in Aconitum species, known for their potent neurotoxic and cardiotoxic effects. While accidental poisonings are relatively rare in Europe, intentional ingestions are more frequently reported. Despite the well-documented clinical effects of aconitine, a comprehensive toxicological investigation including analysis of hair and roots responsible for poisoning has never been reported.</p><p><strong>Methods: </strong>A fatal case of aconitine poisoning was investigated following the ingestion of Aconitum roots. Biological samples (including hair) were analyzed using liquid chromatography-tandem mass spectrometry and liquid chromatography-high-resolution mass spectometry (LC-HRMS). The roots found at the victim's residence were also examined.</p><p><strong>Results: </strong>Aconitine was detected in all tested biological matrices with concentrations of femoral blood and hair of 28.6 ng/mL and 54 pg/mg respectively. The amount of aconitine in the plant root was 0.6 mg/g. Based on the weight and number of roots ingested (as reported by the victim), the estimated dose of aconitine was 12 mg, approximately 2 to 4 times the known lethal dose for an adult.</p><p><strong>Conclusion: </strong>This case presents the first detailed toxicological study of fatal aconitine poisoning that includes both hair and root analysis via LC-HRMS. The results highlight the value of advanced mass spectrometry in forensic detection of alkaloid exposure, while the development of a method for the identification of aconitine in hair could be useful in the future in reconstructing poisoning scenarios and assessing possible repeated exposures.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rafal Typek, Michal P Dybowski, Andrzej L Dawidowicz
{"title":"Cyclization of γ-hydroxybutyric acid (GHBA) as a strategy to enhance its signal in gas chromatography analysis.","authors":"Rafal Typek, Michal P Dybowski, Andrzej L Dawidowicz","doi":"10.1007/s11419-025-00738-z","DOIUrl":"https://doi.org/10.1007/s11419-025-00738-z","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this work is to investigate whether precyclization of γ-hydroxybutyric acid (GABA) allows for increasing its gas chromatography (GC) signal, and if so, is it a more effective way to increase the signal of this compound than its silylation or methylation?</p><p><strong>Methods: </strong>Gas chromatography-mass spectrometry (GC-MS) and GC with flame ionization detection (GC-FID) response to GHBA before and after silylation, methylation, and cyclization were compared. The impact of injector temperature on GHBA and γ-butyrolactone (GBL) signals was assessed. Fourier transformed infra-red spectroscopy was used to examine the formation of macromolecular derivatives in the injector.</p><p><strong>Results: </strong>GHBA shows a lower GC signal than GBL due to partial polycondensation into a non-volatile polyester in the injector. Validation data were established for GHBA after each derivatization. Silylation and methylation reduced the limit of detection (LOD) by approximately 1.5- and 1.3-fold, respectively, whereas pre-cyclization led to at least a 4.6-fold decrease in LOD.</p><p><strong>Conclusions: </strong>The present study elucidates the reasons behind the low GHBA signal observed in GC analysis and, consequently, supports the recommendation to perform pre-cyclization of this compound prior to analysis. Furthermore, the findings demonstrate that although signal enhancement of GHBA can be achieved through silylation or methylation, the most substantial increase is observed following its cyclization during sample preparation. The proposed in this paper cyclization procedure is both remarkably simple and highly effective, allowing for reliable quantification of this hydroxycarboxylic acid in a variety of matrices, including plasma, urine, wine, beer, and orange juice.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a rapid targeted and non-targeted analysis method for etomidate and its structural analogues by ambient flame ionization mass spectrometry.","authors":"Meiting Lin, Miao Zhang, Zhen Zhang, Ping Xiang, Yunli Zhao, Junbo Zhao","doi":"10.1007/s11419-025-00737-0","DOIUrl":"https://doi.org/10.1007/s11419-025-00737-0","url":null,"abstract":"<p><strong>Purpose: </strong>Etomidate, which is a psychoactive drug with an anesthetic effect, is used as a substitute for expensive mainstream drugs. There has been a trend toward abuse of etomidate and its emerging structural analogues now. Faced with a large number of samples, a rapid and effective detection method is needed.</p><p><strong>Methods: </strong>In this study, ambient flame ionization (AFI) coupled with LTQ-Orbitrap mass spectrometry was used to analyze etomidate and its structural analogues in urine. It can realize detection in less than 0.2 min without sample preparation.</p><p><strong>Results: </strong>Ideal analysis conditions were obtained by optimizing various parameters and analytical performance was validated. The isomers (isopropoxate and propoxate) can be distinguished by ion abundance ratios. Positive samples (n = 75) were analyzed very efficiently and successfully from plenty of authentic specimens (n = 116). Statistical analysis was conducted on drug types, age, and gender of drug users. A new structural analogue was discovered in one of the samples, which was a very crucial discovery. That meant the market may face with the emergence of new structural analogues.</p><p><strong>Conclusions: </strong>This study can satisfy both targeted and non-targeted screening, which provides support for timely monitoring and detection of novel drugs and offers a wider range of method choices for forensic laboratories. It can also better cope with the current situation of drug control and combat crimes related to new types of drugs.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Innovative applications of nanotechnology in enhancing forensic science investigations.","authors":"Asmita Podder, Agnishwar Girigoswami, Koyeli Girigoswami","doi":"10.1007/s11419-025-00734-3","DOIUrl":"https://doi.org/10.1007/s11419-025-00734-3","url":null,"abstract":"<p><strong>Purpose: </strong>Forensics, along with the implementation of techniques from nanosciences, has brought about a change in the domain of forensic science and criminal investigation. It has brought about a positive change in the criminal investigation framework by making investigation more efficient and to-the-point.</p><p><strong>Methods: </strong>This paper reviews the nanotechnology-based techniques that are introduced in forensic science to unravel the mysteries behind crimes as it highlights various kinds of nano-sized particles, nanodevices along with their applications that the forensic experts use to analyze the evidences collected from the crime scenes. Google scholar, PubMed, and Scopus search engines are used to select the related articles to write this review paper.</p><p><strong>Results: </strong>DNA analysis, fingerprint detection, drug detection, explosive analysis, blood stain analysis, time since death estimation, and analysis of counterfeit documents are some of the sectors in which nanotechnology has made notable contributions.</p><p><strong>Conclusion: </strong>As the paper unfolds, it makes sure that the readers get the taste of both the worlds, and that it helps them grasp the concept and idea behind the techniques used to make a change across the globe.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of various internal standards for quantification of dextromethorphan and diphenhydramine in plasma: a fatal overdose case of a mid-teenager caused by personally imported and over-the-counter medicines.","authors":"Yujin Natori, Hayato Miura, Takashi Yoshimoto, Akira Ishii","doi":"10.1007/s11419-025-00736-1","DOIUrl":"https://doi.org/10.1007/s11419-025-00736-1","url":null,"abstract":"<p><strong>Purpose: </strong>Over-the-counter medicines are commonly used for recreational and suicidal overdoses, a global problem. Some of these are easily obtained via the Internet. In cases of intoxication, drug quantification is necessary to estimate the cause of death. Stable isotope compounds are recommended as internal standards (IS) for analyzing drugs; however, it is difficult for individual laboratories to obtain isotopes for all analytes due to cost and availability. Therefore, alternative IS selection is important for practicality. Here, we quantified diphenhydramine and dextromethorphan concentrations in plasma from several collection sites in a fatal intoxication case, and assessed various IS performance based on structural similarities and retention time.</p><p><strong>Methods: </strong>A mid-teenager died from intoxication of personally imported dextromethorphan and Over-the-counter diphenhydramine. To quantify these drugs, we selected morphine-d<sub>3</sub>, dihydrocodeine, diphenhydramine-d<sub>3</sub>, mianserin-d<sub>3</sub>, and diazepam-d<sub>5</sub> as alternative IS and evaluated. After selecting the most suitable IS, we quantified dextromethorphan and diphenhydramine concentrations in twelve plasma samples from the victim by liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>Recovery rates were 80.7-105.5%, except for morphine-d<sub>3</sub> (47.8%) and dihydrocodeine (64.8%). Matrix effects were 75.7-103.2%. The intra-day accuracies and precisions were 86.4-119.5% and 0.27-12.2%, respectively. The inter-day accuracies were 81.2-119.8%, and the precisions were 0.80-9.44%. The validation study showed that diphenhydramine-d<sub>3</sub> was the most suitable IS. Finally, plasma concentrations of dextromethorphan and diphenhydramine were 3.74-10.3 µg/mL and 15.6-52.9 µg/mL, respectively.</p><p><strong>Conclusions: </strong>The concentrations of both drugs in plasma samples were estimated to cause death. When using an alternative IS, a validation study is needed to select the optimal IS.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuki Azuma, Misa Tanaka, Akiko Asada, Takahiro Doi
{"title":"In vitro metabolic fate of 1-[3-(trimethylsilyl)propanoyl] lysergic acid diethylamide (1S-LSD), a silicon-containing LSD analog.","authors":"Yuki Azuma, Misa Tanaka, Akiko Asada, Takahiro Doi","doi":"10.1007/s11419-025-00735-2","DOIUrl":"10.1007/s11419-025-00735-2","url":null,"abstract":"<p><strong>Purpose: </strong>A new lysergic acid diethylamide (LSD) analog has recently been identified, 1-[3-(Trimethylsilyl)propanoyl] LSD (1S-LSD), characterized by a silicon-containing acyl moiety. In the proof of LSD analog consumption, direct detection of the parent compound in urine or blood can be challenging; therefore, characteristic metabolites as consumption markers should be detected. However, the metabolic fate is unclear. This study aimed to characterize the metabolic properties of 1S-LSD.</p><p><strong>Methods: </strong>The synthesized 1S-LSD was incubated with human liver microsomes. The obtained metabolites were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry.</p><p><strong>Results: </strong>The parent compound was metabolized at a moderately rapid rate, with the early formation of LSD. Sixty-two metabolites were observed, and a metabolic pathway was proposed. The major metabolites were compounds with hydroxyl groups in the 3-silylpropanoyl moiety. Five metabolites were relatively abundant and retained their 3-silylpropanoyl moieties: N-deethylated 1S-LSD (Si04), N-deethylated and silanolized 1S-LSD (Si06), N-deethylated and monohydroxylated 1S-LSD (Si09 and Si11), and silanolized 1S-LSD (Si21).</p><p><strong>Conclusions: </strong>The metabolic fate of 1S-LSD, an abused drug containing silicon, was characterized for the first time. The diverse metabolic pathways will help better understand the metabolic processes of not only 1S-LSD but also N<sup>1</sup>-acylated LSD analogs and compounds with trimethylsilyl groups. Si04, Si06, Si09, Si11, and Si21 are potential target analytes for proving 1S-LSD consumption.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}