Nadja Walle , Adrian A. Doerr , Benjamin Peters , Matthias W. Laschke , Michael D. Menger , Peter H. Schmidt , Markus R. Meyer , Nadine Schaefer
{"title":"合成大麻素 cumyl-5F-P7AICA 及其 N-戊酸代谢物在死后的浓度变化是否取决于环境条件?- 猪肺部给药后的系统研究","authors":"Nadja Walle , Adrian A. Doerr , Benjamin Peters , Matthias W. Laschke , Michael D. Menger , Peter H. Schmidt , Markus R. Meyer , Nadine Schaefer","doi":"10.1016/j.toxlet.2024.10.006","DOIUrl":null,"url":null,"abstract":"<div><div>The number of fatal cases involving synthetic cannabinoids (SCs) is increasing. However, interpretation of postmortem (PM) toxicological findings is challenging, due to unknown PM intervals and possible redistribution processes or instabilities. Only sparse data on SCs are available. Therefore, a controlled pig study was performed to determine the PM stability of <em>cumyl</em>-5F-P7AICA under different environmental conditions. Ten pigs inhalatively received 200 µg/kg body weight <em>cumyl</em>-5F-P7AICA each. Six hours later, they were euthanized and biopsies of the main tissues and body fluids were taken. Animals were stored in air or water (n=5 each) and samples were repeatedly taken for three days. Quantification of <em>cumyl</em>-5F-P7AICA and its <em>N</em>-pentanoic acid metabolite (NPA) was performed using standard addition or a fully validated method (blood) followed by LC-MS/MS. Time-dependent concentration changes of <em>cumyl</em>-5F-P7AICA were observed in liver, bile fluid and muscle specimens at both conditions. Concentrations of NPA only changed considerably in duodenum content of animals stored in air. Environment-dependent concentrations changes were only observed for <em>cumyl</em>-5F-P7AICA in kidney and the NPA metabolite in duodenum content. Overall, <em>cumyl</em>-5F-P7AICA and its metabolite seem to be quite stable in PM specimens. Hence, also central blood might be analyzed, if no peripheral blood is available.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"401 ","pages":"Pages 170-180"},"PeriodicalIF":2.9000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Are the postmortem concentration changes of the synthetic cannabinoid cumyl-5F-P7AICA and its N-pentanoic acid metabolite dependent on the environmental conditions? – A systematic study following pulmonary administration to pigs\",\"authors\":\"Nadja Walle , Adrian A. Doerr , Benjamin Peters , Matthias W. Laschke , Michael D. Menger , Peter H. Schmidt , Markus R. Meyer , Nadine Schaefer\",\"doi\":\"10.1016/j.toxlet.2024.10.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The number of fatal cases involving synthetic cannabinoids (SCs) is increasing. However, interpretation of postmortem (PM) toxicological findings is challenging, due to unknown PM intervals and possible redistribution processes or instabilities. Only sparse data on SCs are available. Therefore, a controlled pig study was performed to determine the PM stability of <em>cumyl</em>-5F-P7AICA under different environmental conditions. Ten pigs inhalatively received 200 µg/kg body weight <em>cumyl</em>-5F-P7AICA each. Six hours later, they were euthanized and biopsies of the main tissues and body fluids were taken. Animals were stored in air or water (n=5 each) and samples were repeatedly taken for three days. Quantification of <em>cumyl</em>-5F-P7AICA and its <em>N</em>-pentanoic acid metabolite (NPA) was performed using standard addition or a fully validated method (blood) followed by LC-MS/MS. Time-dependent concentration changes of <em>cumyl</em>-5F-P7AICA were observed in liver, bile fluid and muscle specimens at both conditions. Concentrations of NPA only changed considerably in duodenum content of animals stored in air. Environment-dependent concentrations changes were only observed for <em>cumyl</em>-5F-P7AICA in kidney and the NPA metabolite in duodenum content. Overall, <em>cumyl</em>-5F-P7AICA and its metabolite seem to be quite stable in PM specimens. Hence, also central blood might be analyzed, if no peripheral blood is available.</div></div>\",\"PeriodicalId\":23206,\"journal\":{\"name\":\"Toxicology letters\",\"volume\":\"401 \",\"pages\":\"Pages 170-180\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S037842742402040X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S037842742402040X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Are the postmortem concentration changes of the synthetic cannabinoid cumyl-5F-P7AICA and its N-pentanoic acid metabolite dependent on the environmental conditions? – A systematic study following pulmonary administration to pigs
The number of fatal cases involving synthetic cannabinoids (SCs) is increasing. However, interpretation of postmortem (PM) toxicological findings is challenging, due to unknown PM intervals and possible redistribution processes or instabilities. Only sparse data on SCs are available. Therefore, a controlled pig study was performed to determine the PM stability of cumyl-5F-P7AICA under different environmental conditions. Ten pigs inhalatively received 200 µg/kg body weight cumyl-5F-P7AICA each. Six hours later, they were euthanized and biopsies of the main tissues and body fluids were taken. Animals were stored in air or water (n=5 each) and samples were repeatedly taken for three days. Quantification of cumyl-5F-P7AICA and its N-pentanoic acid metabolite (NPA) was performed using standard addition or a fully validated method (blood) followed by LC-MS/MS. Time-dependent concentration changes of cumyl-5F-P7AICA were observed in liver, bile fluid and muscle specimens at both conditions. Concentrations of NPA only changed considerably in duodenum content of animals stored in air. Environment-dependent concentrations changes were only observed for cumyl-5F-P7AICA in kidney and the NPA metabolite in duodenum content. Overall, cumyl-5F-P7AICA and its metabolite seem to be quite stable in PM specimens. Hence, also central blood might be analyzed, if no peripheral blood is available.