Pub Date : 2025-02-04DOI: 10.1016/j.jpba.2025.116735
Ming Li , Hua Sun , Jin-Ling Song , Xing Sun , Wei Li
I3,II8-biapigenin is a biflavonoid compound with diverse pharmacological effects. The present study aimed to investigate the glucuronidation of I3,II8-biapigenin in the human liver microsomes (HLMs) and recombinant human UDP-glucuronosyltransferases (UGTs). Three glucuronidation metabolites of I3,II8-biapigenin were detected in HLMs. Both recombinant human UGTs and chemical inhibitors studies demonstrated that UGT1A1, UGT1A3, UGT1A9 and UGT1A10 were involved in the glucuronidation of I3,II8-biapigenin. The present investigation provided information for the drug-drug interaction potentials of I3,II8-biapigenin when co-administrated with UGTs inhibitors or inducers.
{"title":"Identification of human UDP-glucuronosyltransferases involved in I3,II8-biapigenin glucuronidation in Vitro","authors":"Ming Li , Hua Sun , Jin-Ling Song , Xing Sun , Wei Li","doi":"10.1016/j.jpba.2025.116735","DOIUrl":"10.1016/j.jpba.2025.116735","url":null,"abstract":"<div><div>I3,II8-biapigenin is a biflavonoid compound with diverse pharmacological effects. The present study aimed to investigate the glucuronidation of I3,II8-biapigenin in the human liver microsomes (HLMs) and recombinant human UDP-glucuronosyltransferases (UGTs). Three glucuronidation metabolites of I3,II8-biapigenin were detected in HLMs. Both recombinant human UGTs and chemical inhibitors studies demonstrated that UGT1A1, UGT1A3, UGT1A9 and UGT1A10 were involved in the glucuronidation of I3,II8-biapigenin. The present investigation provided information for the drug-drug interaction potentials of I3,II8-biapigenin when co-administrated with UGTs inhibitors or inducers.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116735"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.jpba.2025.116736
Weiwei Li , Jing Zhu , Ting Zhou , Ziwen Jin
Yinchenhao decoction (YCHD) has been used for the treatment of cholestasis for more than 1000 years with clear clinical efficacy. However, its active compounds and pharmacological mechanism against cholestasis are unclear. In this study, an integrated strategy of network pharmacology, lipidomics, metabolomics, and molecular docking were performed to elucidate the mechanism of YCHD’s anti-cholestasis effect. Network pharmacology demonstrated YCHD mainly modulated lipid and atherosclerosis signaling pathways with the involvement of NF-κB, TNF, MAPK, and PI3K/AKT signaling pathways. In vivo experiments, male C57BL/6 J mice model of cholestasis was established by alpha-naphthyl isothiocyanate (ANIT), and were treated with different dosages (3 g/kg and 9 g/kg) of YCHD for one week. Ursodeoxycholic acid (UDCA) was used as a positive control. The in vivo experiments verified the ameliorative effect of YCHD on inflammation, hepatocellular injury and cholestasis. Furthermore, lipidomics and metabolomics research showed that YCHD could improve the metabolism disorder of glycerolipid, glycerophospholipid and amino acids. Subsequently, further WB and molecular docking validation experiments showed that the active compounds in YCHD have regulatory effects on the PPARγ/NF-κB/JNK pathway, the core pathway in lipid and atherosclerosis pathways, thereby inhibiting inflammatory response and improving lipid metabolism disorders. This study could provide evidence of the molecular mechanism and material basis of YCHD in treating cholestasis. This study also provided new research ideas for the discovery of active ingredients in traditional Chinese medicine formulas for the treatment of cholestasis.
{"title":"Exploring the mechanisms of Yinchenhao decoction against ANIT-induced cholestatic liver injury by lipidomics, metabolomics and network pharmacology","authors":"Weiwei Li , Jing Zhu , Ting Zhou , Ziwen Jin","doi":"10.1016/j.jpba.2025.116736","DOIUrl":"10.1016/j.jpba.2025.116736","url":null,"abstract":"<div><div>Yinchenhao decoction (YCHD) has been used for the treatment of cholestasis for more than 1000 years with clear clinical efficacy. However, its active compounds and pharmacological mechanism against cholestasis are unclear. In this study, an integrated strategy of network pharmacology, lipidomics, metabolomics, and molecular docking were performed to elucidate the mechanism of YCHD’s anti-cholestasis effect. Network pharmacology demonstrated YCHD mainly modulated lipid and atherosclerosis signaling pathways with the involvement of NF-κB, TNF, MAPK, and PI3K/AKT signaling pathways. In <em>vivo</em> experiments, male C57BL/6 J mice model of cholestasis was established by alpha-naphthyl isothiocyanate (ANIT), and were treated with different dosages (3 g/kg and 9 g/kg) of YCHD for one week. Ursodeoxycholic acid (UDCA) was used as a positive control. The <em>in vivo</em> experiments verified the ameliorative effect of YCHD on inflammation, hepatocellular injury and cholestasis. Furthermore, lipidomics and metabolomics research showed that YCHD could improve the metabolism disorder of glycerolipid, glycerophospholipid and amino acids. Subsequently, further WB and molecular docking validation experiments showed that the active compounds in YCHD have regulatory effects on the PPARγ/NF-κB/JNK pathway, the core pathway in lipid and atherosclerosis pathways, thereby inhibiting inflammatory response and improving lipid metabolism disorders. This study could provide evidence of the molecular mechanism and material basis of YCHD in treating cholestasis. This study also provided new research ideas for the discovery of active ingredients in traditional Chinese medicine formulas for the treatment of cholestasis.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116736"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143289644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.jpba.2025.116729
Xiaoqian Chen , Luyao Yu , Yingxia Guo , Jiansong You , Meiyun Shi , Yalin Xi , Lei Yin
An analytical assay based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique for absolute quantification of vancomycin in complexed biological matrix was developed in this study. Reversed phase column with gradient elution was chosen for chromatographic separation of vancomycin and internal standard (IS) norancomycin. Sample pretreatment was performed by micro-solid phase extraction (μ-SPE) with Oasis® MAX μElution Plate (I.D., 30 μm). Multiple reaction monitoring (MRM) transition was chosen for monitoring of the analytes. For vancomycin, mass-to-charge ratio (m/z) of the MRM transition was 725.3→144.1; For norvancomycin, m/z of the MRM transition was 718.3→144.2. The running time was 3 minutes for each sample. The UHPLC-MS/MS method showed a good linear relationship (R2≥0.995) in the concentration range of 0.5–100 μg/mL. The intra- and inter-day accuracies (relative error, RE) are within the range of −3.44 %-1.50 % and precisions are between 3.48 % and 10.19 %. μ-SPE could enrich the analytes and decrease the endogenous interferences, thereby improving the selectivity and sensitivity of the method. The analytical assay is selective, accurate and reproducible. The assay was successfully applied to therapeutic drug monitoring of vancomycin in clinical application.
{"title":"High throughput analysis of vancomycin in human plasma by UHPLC-MS/MS","authors":"Xiaoqian Chen , Luyao Yu , Yingxia Guo , Jiansong You , Meiyun Shi , Yalin Xi , Lei Yin","doi":"10.1016/j.jpba.2025.116729","DOIUrl":"10.1016/j.jpba.2025.116729","url":null,"abstract":"<div><div>An analytical assay based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique for absolute quantification of vancomycin in complexed biological matrix was developed in this study. Reversed phase column with gradient elution was chosen for chromatographic separation of vancomycin and internal standard (IS) norancomycin. Sample pretreatment was performed by micro-solid phase extraction (μ-SPE) with Oasis® MAX μElution Plate (I.D., 30 μm). Multiple reaction monitoring (MRM) transition was chosen for monitoring of the analytes. For vancomycin, mass-to-charge ratio (<em>m/z</em>) of the MRM transition was 725.3→144.1; For norvancomycin, <em>m/z</em> of the MRM transition was 718.3→144.2. The running time was 3 minutes for each sample. The UHPLC-MS/MS method showed a good linear relationship (R<sup>2</sup>≥0.995) in the concentration range of 0.5–100 μg/mL. The intra- and inter-day accuracies (relative error, RE) are within the range of −3.44 %-1.50 % and precisions are between 3.48 % and 10.19 %. μ-SPE could enrich the analytes and decrease the endogenous interferences, thereby improving the selectivity and sensitivity of the method. The analytical assay is selective, accurate and reproducible. The assay was successfully applied to therapeutic drug monitoring of vancomycin in clinical application.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116729"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.jpba.2025.116734
Xiaolin Wu , Qiao Yu , Yuzhao Hou , Xuemei Zhang , Simon Sani Ocholi , Liming Wang , Ziping Yan , Jie Li , Lifeng Han
Cholestatic liver disease(CLD) is caused by impaired bile flow due to obstruction of the biliary tract, and long-term exposure to bile acids in the liver triggers inflammation, eventually leading to liver toxicity and liver fibrosis. Emodin-8-O-β-D-glucopyranoside(EG) is anthraquinone compound that is widely found in traditional Chinese medicine. It possessed antioxidative and anti-inflammatory activities. However, the effect of EG on cholestatic liver injury(CLI) has not been explored. In this study, Alpha-naphthyl isothiocyanate(ANIT)-induced CLI mice were used to investigate the anti-cholestasis and hepatoprotective effects of EG through serum biochemical index detection, non-targeted metabolomics, lipidomics, and intestinal flora 16S rRNA sequencing. The results suggested that EG restores homeostasis of the gut microbiome while regulating bile acids metabolism and lipid-related metabolic pathways to reduce liver damage in ANIT-induced cholestasis. This study provides a new perspective on the mechanism of EG, and help offer a more natural approach to managing liver damage.
{"title":"Emodin-8-O-β-D-glucopyranoside alleviates cholestasis by maintaining intestinal homeostasis and regulating lipids and bile acids metabolism in mice","authors":"Xiaolin Wu , Qiao Yu , Yuzhao Hou , Xuemei Zhang , Simon Sani Ocholi , Liming Wang , Ziping Yan , Jie Li , Lifeng Han","doi":"10.1016/j.jpba.2025.116734","DOIUrl":"10.1016/j.jpba.2025.116734","url":null,"abstract":"<div><div>Cholestatic liver disease(CLD) is caused by impaired bile flow due to obstruction of the biliary tract, and long-term exposure to bile acids in the liver triggers inflammation, eventually leading to liver toxicity and liver fibrosis. Emodin-8-<em>O-β</em>-D-glucopyranoside(EG) is anthraquinone compound that is widely found in traditional Chinese medicine. It possessed antioxidative and anti-inflammatory activities. However, the effect of EG on cholestatic liver injury(CLI) has not been explored. In this study, Alpha-naphthyl isothiocyanate(ANIT)-induced CLI mice were used to investigate the anti-cholestasis and hepatoprotective effects of EG through serum biochemical index detection, non-targeted metabolomics, lipidomics, and intestinal flora 16S rRNA sequencing. The results suggested that EG restores homeostasis of the gut microbiome while regulating bile acids metabolism and lipid-related metabolic pathways to reduce liver damage in ANIT-induced cholestasis. This study provides a new perspective on the mechanism of EG, and help offer a more natural approach to managing liver damage.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116734"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the context of forensic medicine, the differential diagnosis between mechanical asphyxia and sudden cardiac death is very important regarding the establishment of the cause of death. Traditional autopsy findings have generally been very nonspecific; accordingly, highlighting the need for more specific molecular biomarkers. This study employed four-dimensional data-independent acquisition (4D-DIA) proteomics technology, in combination with both animal models and human samples, to conduct a comprehensive protein expression analysis of cardiac tissues, identifying 7557 proteins, among which 142 shared differentially expressed proteins (DEPS) were screened out. Based on the protein interaction network and through rigorous screening, this study identified three proteins, namely TNF receptor-associated factor 2 (TRAF2), Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G), and translocase of inner mitochondrial membrane 17 homolog A (TIMM17A), as biomarkers for differentiating mechanical asphyxia from sudden cardiac death. Further verification using Western Blot (WB) and immunohistochemistry (IHC) proved the differential expression of these biomarkers in both animal and human samples. These findings, besides deepening the molecular understanding of the pathophysiological differences between sudden cardiac death and mechanical asphyxia, also provided new biomarkers for forensic applications that could enable the improvement of accuracy and reliability in the determination of the cause of death.
{"title":"Identification of TRAF2, CAMK2G, and TIMM17A as biomarkers distinguishing mechanical asphyxia from sudden cardiac death base on 4D-DIA Proteomics: A pilot study","authors":"Yuebing Huang, Hai Qiu, Wen Chen, Zilin Meng, Yu Cai, Dongfang Qiao, Xia Yue","doi":"10.1016/j.jpba.2025.116730","DOIUrl":"10.1016/j.jpba.2025.116730","url":null,"abstract":"<div><div>In the context of forensic medicine, the differential diagnosis between mechanical asphyxia and sudden cardiac death is very important regarding the establishment of the cause of death. Traditional autopsy findings have generally been very nonspecific; accordingly, highlighting the need for more specific molecular biomarkers. This study employed four-dimensional data-independent acquisition (4D-DIA) proteomics technology, in combination with both animal models and human samples, to conduct a comprehensive protein expression analysis of cardiac tissues, identifying 7557 proteins, among which 142 shared differentially expressed proteins (DEPS) were screened out. Based on the protein interaction network and through rigorous screening, this study identified three proteins, namely TNF receptor-associated factor 2 (TRAF2), Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G), and translocase of inner mitochondrial membrane 17 homolog A (TIMM17A), as biomarkers for differentiating mechanical asphyxia from sudden cardiac death. Further verification using Western Blot (WB) and immunohistochemistry (IHC) proved the differential expression of these biomarkers in both animal and human samples. These findings, besides deepening the molecular understanding of the pathophysiological differences between sudden cardiac death and mechanical asphyxia, also provided new biomarkers for forensic applications that could enable the improvement of accuracy and reliability in the determination of the cause of death.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116730"},"PeriodicalIF":3.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143289645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/j.jpba.2025.116727
Abdellatif Ait Lahcen, Gymama Slaughter
Monitoring human immunodeficiency virus (HIV) and anti-HIV drugs is critical for optimizing treatment outcomes and preventing drug resistance. Accurate detection and quantification of anti-HIV drugs are essential to ensure appropriate dosing, enhancing patient care and therapeutic efficacy. Electrochemical biosensors have emerged as a pivotal tool in this context, offering high sensitivity, specificity, and rapid response times. Leveraging advancements in nanomaterials, these sensors provide reliable and efficient solutions for point-of-care (POC) applications in clinical and environmental settings. This review presents a comprehensive analysis of recent innovations in electrochemical sensor technologies for anti-HIV drug detection and quantification, focusing on nanomaterial-based platforms. It addresses the challenges of developing and implementing these technologies, including matrix effects, stability, and scalability. Furthermore, the review explores future directions, emphasizing the integration of sensors into POC systems and their potential to revolutionize personalized HIV treatment and pharmaceutical monitoring.
{"title":"Nanomaterial-based electrochemical sensors for anti-HIV drug monitoring: Innovations, challenges, and prospects","authors":"Abdellatif Ait Lahcen, Gymama Slaughter","doi":"10.1016/j.jpba.2025.116727","DOIUrl":"10.1016/j.jpba.2025.116727","url":null,"abstract":"<div><div>Monitoring human immunodeficiency virus (HIV) and anti-HIV drugs is critical for optimizing treatment outcomes and preventing drug resistance. Accurate detection and quantification of anti-HIV drugs are essential to ensure appropriate dosing, enhancing patient care and therapeutic efficacy. Electrochemical biosensors have emerged as a pivotal tool in this context, offering high sensitivity, specificity, and rapid response times. Leveraging advancements in nanomaterials, these sensors provide reliable and efficient solutions for point-of-care (POC) applications in clinical and environmental settings. This review presents a comprehensive analysis of recent innovations in electrochemical sensor technologies for anti-HIV drug detection and quantification, focusing on nanomaterial-based platforms. It addresses the challenges of developing and implementing these technologies, including matrix effects, stability, and scalability. Furthermore, the review explores future directions, emphasizing the integration of sensors into POC systems and their potential to revolutionize personalized HIV treatment and pharmaceutical monitoring.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116727"},"PeriodicalIF":3.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143179315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jpba.2025.116717
Xuan Wang , Yuanfeng Lyu , Sau Wan Cheng , Tsz Fung Tsang , Ka Chun Chong , Siaw Shi Boon , Xiao Yang , Christopher KC Lai , Paul KS Chan , Zhong Zuo
The interaction between marketed drugs and the gut microbiome is increasingly being recognized, and it is now known that enzymes produced by the bacteria in the human gut can degrade psychotropic drugs. However, the degree of inter-individual variation in their metabolism remains largely unknown. Here, we present a simple model for detecting individual drug-microbiome interaction using fecalase. We incubated fecalase prepared from freshly collected stool samples from healthy volunteers (n = 18) and incubated with nine selected psychotropic medications. We proved fecalase retained enzymatic activities and showed the degree of drug degradation differed significantly for different psychotropic drugs, and there was significant inter-individual variation in the metabolism of phenytoin, amitriptyline, and chlorpromazine with the inter-individual point difference between the strongest and weakest metabolizer of 85 %, 39 %, and 30 % respectively. These findings highlight the potential of fecalase as a model for studying personalized drug metabolism and underscore the importance of considering gut microbiome variability in pharmacological research.
{"title":"Inter-individual variability in the metabolism of psychotropic drugs by the enzyme activities from the human gut microbiome","authors":"Xuan Wang , Yuanfeng Lyu , Sau Wan Cheng , Tsz Fung Tsang , Ka Chun Chong , Siaw Shi Boon , Xiao Yang , Christopher KC Lai , Paul KS Chan , Zhong Zuo","doi":"10.1016/j.jpba.2025.116717","DOIUrl":"10.1016/j.jpba.2025.116717","url":null,"abstract":"<div><div>The interaction between marketed drugs and the gut microbiome is increasingly being recognized, and it is now known that enzymes produced by the bacteria in the human gut can degrade psychotropic drugs. However, the degree of inter-individual variation in their metabolism remains largely unknown. Here, we present a simple model for detecting individual drug-microbiome interaction using fecalase. We incubated fecalase prepared from freshly collected stool samples from healthy volunteers (n = 18) and incubated with nine selected psychotropic medications. We proved fecalase retained enzymatic activities and showed the degree of drug degradation differed significantly for different psychotropic drugs, and there was significant inter-individual variation in the metabolism of phenytoin, amitriptyline, and chlorpromazine with the inter-individual point difference between the strongest and weakest metabolizer of 85 %, 39 %, and 30 % respectively. These findings highlight the potential of fecalase as a model for studying personalized drug metabolism and underscore the importance of considering gut microbiome variability in pharmacological research.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116717"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143352318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.jpba.2025.116707
Guoqing Gao , Shuo Yang , Xin Wang , Ping Xiang , Liting Ma , Fang Yan , Yan Shi
Nitazenes, a new class of potent synthetic opioids characterized by a 2-benzyl-benzimidazole structural core, have emerged on the illicit drug market following fentanyl. Compared to traditional opioids, nitazenes pose heightened risks of respiratory depression and central nervous system suppression. Due to the ease of modification of its parent nucleus, abusers and dealers can rapidly synthesize new structural analogs that fall outside the drug control catalog. Consequently, multiple isomers of nitazenes have emerged, causing significant interference in forensic practices. As an increasing number of poisoning and fatality cases were associated with nitazenes, there is an urgent need for developing an analytical method that can effectively address the challenges currently encountered in their identification in forensic practices. In this study, we established and validated a simple and high-efficiency ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for detecting 17 nitazenes in human hair. All analytes were separated in 6.5 min on a biphenyl column with simultaneous separation of six groups of isomers. Method validation demonstrated linear calibration over the range of 5–1000 pg/mg (r > 0.995), with limits of detection (LODs) ranging from 1 to 15 pg/mg and limits of quantification (LOQs) ranging from 5 to 20 pg/mg. The method also exhibited precision (<15 %) and accuracy ( ± 15 %), along with excellent recovery, acceptable matrix effects, and good stability at 4 ℃ for at least 72 h. When applied to authentic cases, this method successfully identified two positive hair samples and N,N-dimethylamino etonitazene was detected at concentrations of 1528.5 pg/mg and 463.9 pg/mg, respectively. This method provides technical support for the rapid and accurate detection of nitazenes, better meeting the needs of anti-drug operations and forensic practice.
{"title":"UHPLC-MS/MS-based analysis of 17 nitazenes in human hair for practical forensic casework with simultaneous separation of 6 groups of isomers","authors":"Guoqing Gao , Shuo Yang , Xin Wang , Ping Xiang , Liting Ma , Fang Yan , Yan Shi","doi":"10.1016/j.jpba.2025.116707","DOIUrl":"10.1016/j.jpba.2025.116707","url":null,"abstract":"<div><div>Nitazenes, a new class of potent synthetic opioids characterized by a 2-benzyl-benzimidazole structural core, have emerged on the illicit drug market following fentanyl. Compared to traditional opioids, nitazenes pose heightened risks of respiratory depression and central nervous system suppression. Due to the ease of modification of its parent nucleus, abusers and dealers can rapidly synthesize new structural analogs that fall outside the drug control catalog. Consequently, multiple isomers of nitazenes have emerged, causing significant interference in forensic practices. As an increasing number of poisoning and fatality cases were associated with nitazenes, there is an urgent need for developing an analytical method that can effectively address the challenges currently encountered in their identification in forensic practices. In this study, we established and validated a simple and high-efficiency ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for detecting 17 nitazenes in human hair. All analytes were separated in 6.5 min on a biphenyl column with simultaneous separation of six groups of isomers. Method validation demonstrated linear calibration over the range of 5–1000 pg/mg (r > 0.995), with limits of detection (LODs) ranging from 1 to 15 pg/mg and limits of quantification (LOQs) ranging from 5 to 20 pg/mg. The method also exhibited precision (<15 %) and accuracy ( ± 15 %), along with excellent recovery, acceptable matrix effects, and good stability at 4 ℃ for at least 72 h. When applied to authentic cases, this method successfully identified two positive hair samples and N,N-dimethylamino etonitazene was detected at concentrations of 1528.5 pg/mg and 463.9 pg/mg<sup>,</sup> respectively. This method provides technical support for the rapid and accurate detection of nitazenes, better meeting the needs of anti-drug operations and forensic practice.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116707"},"PeriodicalIF":3.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.jpba.2025.116720
Jean Simon Thodhekes Yao , Yoann Ladner , N.’Cho Christophe Amin , Catherine Perrin
This review focuses on the use of Salting-Out Assisted Liquid-Liquid Extraction (SALLE) for blood sample processing prior analysis, exploring its principles, optimization parameters, and coupling with analytical techniques. SALLE is favored for its simplicity, cost-effectiveness, and rapid execution using the salting-out effect to induce phase separation in mixtures of aqueous samples and water-miscible organic solvents. The review categorizes and discusses the different types of blood samples, the main salts and solvents used, and the parameters affecting the extraction efficiency, such as solvent and salt type as well as ionic strength, pH, vortex mixing and centrifugation time. Advantages of SALLE over traditional methods like solid-phase extraction (SPE) and protein precipitation (PP) are highlighted, emphasizing its environmental friendliness, high extraction efficiency, and ease of automation. By examining recent literature and scientific publications (2014–2024), this review provides a comprehensive understanding of the factors influencing SALLE performance and its application in bioanalysis, particularly when coupled with separative techniques such as liquid chromatography (LC), capillary electrophoresis (CE), and mass spectrometry (MS).
{"title":"Salting-out assisted liquid-liquid extraction (SALLE): Principle, optimization, and applications in blood sample analysis","authors":"Jean Simon Thodhekes Yao , Yoann Ladner , N.’Cho Christophe Amin , Catherine Perrin","doi":"10.1016/j.jpba.2025.116720","DOIUrl":"10.1016/j.jpba.2025.116720","url":null,"abstract":"<div><div>This review focuses on the use of Salting-Out Assisted Liquid-Liquid Extraction (SALLE) for blood sample processing prior analysis, exploring its principles, optimization parameters, and coupling with analytical techniques. SALLE is favored for its simplicity, cost-effectiveness, and rapid execution using the salting-out effect to induce phase separation in mixtures of aqueous samples and water-miscible organic solvents. The review categorizes and discusses the different types of blood samples, the main salts and solvents used, and the parameters affecting the extraction efficiency, such as solvent and salt type as well as ionic strength, pH, vortex mixing and centrifugation time. Advantages of SALLE over traditional methods like solid-phase extraction (SPE) and protein precipitation (PP) are highlighted, emphasizing its environmental friendliness, high extraction efficiency, and ease of automation. By examining recent literature and scientific publications (2014–2024), this review provides a comprehensive understanding of the factors influencing SALLE performance and its application in bioanalysis, particularly when coupled with separative techniques such as liquid chromatography (LC), capillary electrophoresis (CE), and mass spectrometry (MS).</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"257 ","pages":"Article 116720"},"PeriodicalIF":3.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.jpba.2025.116715
Kening Li , Siyu Wang , Weiwei Tang , Yanwen Chen , Bin Li
Complex amine metabolic disorders are implicated in ischemic stroke and can further exacerbate brain damage. Therefore, ameliorating their metabolic disorder would be an effective way to improve recovery from brain damage after ischemia/reperfusion (I/R) injury. In this work, the protective effects of Edaravone (Eda), Ginaton injection (Gin), and their combination (Eda+Gin) against cerebral I/R injury in a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model were preliminarily investigated from the perspective of spatial metabolomics. Compared to single-drug treatment, the optimized combination treatment with Eda and Gin significantly decreased infarct volumes, improved neurological function, and inhibited neuronal damage and glial cell activation in MCAO/R rats. Also, combination treatment could prolong the blood circulation time of quercetin, ginkgolide C, and eight flavonoid glycosides compared to Gin treatment alone. More importantly, the spatial metabolic alterations of amine metabolites in MCAO/R rats before and after drug treatment were comprehensively interrogated using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) coupled with laser-assisted chemical transfer (LACT)-based on tissue chemical derivatization, such as amino acids, dipeptides, tripeptides, neurotransmitters, and the other amine metabolites. MALDI MSI results showed that the drastic metabolic disorders occurred in the cerebral cortex (CTX) and striatum (STR) and combination treatment exerted a better regulatory effect on the perturbed spatial amine metabolism. Therefore, combination treatment with Eda and Gin could significantly reduce ischemic brain damage and correct spatial metabolic disorders of amine metabolites, providing a potential treatment strategy for cerebral I/R injury.
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