Identification and quantification of mepirapim and acetyl fentanyl in authentic human whole blood and urine samples by GC–MS/MS and LC–MS/MS
Tóm tắt
We encountered a curious case in which two male subjects self-administered mepirapim plus acetyl fentanyl by different routes, i.e., intravenously and by inhalation. We have thus established a detailed procedure for quantification of mepirapim and acetyl fentanyl in whole blood and urine specimens using gas chromatography (GC)–tandem mass spectrometry (MS/MS). The GC–MS/MS method was validated for linearity, extraction recovery, accuracy, and precision. Liquid chromatography–MS/MS was also used for identification of the target compounds. Good linearity and reproducibility were achieved in the range of 20–1000 ng/g for both target compounds in both matrices. The concentrations of mepirapim in heart whole blood, femoral vein whole blood, and urine of the deceased individual with administration by intravenous injection were 593, 567, and 527 ng/g, respectively; those of acetyl fentanyl were 155, 125, and 126 ng/g, respectively. The mepirapim and acetyl fentanyl concentrations in the urine specimen of the surviving individual who had administered them by inhalation were 4900 and 570 ng/g, respectively. To our knowledge, with the exception of a brief mention of a mepirapim concentration in a serum sample in emergency medicine, there are no reported data on the identification and quantification of mepirapim in biological samples. Mepirapim is a new synthetic cannabinoid. The concentration profiles of unchanged mepirapim in whole blood and urine were quite different and unique. A detailed clarification of such uniqueness is under way in our laboratory.
Tài liệu tham khảo
Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl)benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281
Gurney SMR, Scott KS, Kacinko SL, Presley BC, Logan BK (2014) Pharmacology, toxicology, and adverse effects of synthetic cannabinoid drugs. Forensic Sci Rev 26:53–78
Katselou M, Papoutsis I, Nikolaou P, Spiliopoulou C, Athanaselis S (2016) Old opioids, new concerns: the case of acetyl fentanyl. Forensic Toxicol 34:201–212
Uchiyama N, Shimokawa Y, Matsuda S, Kawamura M, Kikura-Hanajiri R, Goda Y (2014) Two new synthetic cannabinoids, AM-2201 benzimidazole analog (FUBIMINA) and (4-methylpiperazin-1-yl)(1-pentyl-1H-indol-3-yl)methanone (MEPIRAPIM), and three phenethylamine derivatives, 25H-NBOMe 3,4,5-trimethoxybenzyl analog, 25B-NBOMe, and 2C-N-NBOMe, identified in illegal products. Forensic Toxicol 32:105–111
Cayman chemical (2017) https://www.caymanchem.com/product/15388. Accessed June 2017
Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR (2000) Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding. Drug Alcohol Depend 60:133–140
Higashikawa Y, Suzuki S (2008) Studies on 1-(2-phenethyl)-4-(N-propionylanilino) piperidine (fentanyl) and its related compounds. VI. Structure–analgesic activity relationship for fentanyl, methyl-substituted fentanyls and other analogues. Forensic Toxicol 26:1–5
Stogner JM (2014) The potential threat of acetyl fentanyl: legal issues, contaminated heroin, and acetyl fentanyl “disguised” as other opioids. Ann Emerg Med 64:637–639
Lozier MJ, Boyd M, Stanley C, Ogilvie L, King E, Martin C, Lewis L (2015) Acetyl fentanyl, a novel fentanyl analog, causes 14 overdose deaths in Rhode Island, March-May 2013. J Med Toxicol 11:208–217
Poklis J, Poklis A, Wolf C, Mainland M, Hair L, Devers K, Chrostowski L, Arbefeville E, Merves M, Pearson J (2015) Postmortem tissue distribution of acetyl fentanyl, fentanyl and their respective nor-metabolites analyzed by ultrahigh performance liquid chromatography with tandem mass spectrometry. Forensic Sci Int 257:435–441
McIntyre IM, Trochta A, Gary RD, Malamatos M, Lucas JR (2015) An acute acetyl fentanyl fatality: a case report with postmortem concentrations. J Anal Toxicol 39:490–494
Yonemitsu K, Sasao A, Mishima S, Ohtsu Y, Nishitani Y (2016) A fatal poisoning case by intravenous injection of “bath salts” containing acetyl fentanyl and 4-methoxy PV8. Forensic Sci Int 267:e6–e9
Takase I, Koizumi T, Fujimoto I, Yanai A, Fujimiya T (2016) An autopsy case of acetyl fentanyl intoxication caused by insufflation of ‘designer drugs’. Leg Med 21:38–44
Fort C, Curtis B, Nichols C, Niblo C (2016) Acetyl fentanyl toxicity: two case report. J Anal Toxicol 40:754–757
Cunningham SM, Haikal NA, Kraner JC (2016) Fatal intoxication with acetyl fentanyl. J Forensic Sci 61:S276–S280
Fujita Y, Koeda A, Fujino Y, Onodera M, Kikuchi S, Niitsu H, Iwasaki Y, Usui K, Inoue Y (2016) Clinical and toxicological findings of acute intoxication with synthetic cannabinoids and cathinones. Acute Med Surg 3:230–236
Shanks KG, Dahn T, Terrell AR (2012) Detection of JWH-018 and JWH-073 by UPLC–MS–MS in postmortem whole blood casework. J Anal Toxicol 36:145–152
Behonick G, Shanks KG, Firchau DJ, Mathur G, Lynch CF, Nashelsky M, Jaskierny DJ, Meroueh C (2014) Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22. J Anal Toxicol 38:559–562
Hermanns-Clausen M, Kneisel S, Hutter M, Szabo B, Auwärter V (2013) Acute intoxication by synthetic cannabinoids—four case reports. Drug Test Anal 5:790–794
Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (2017) Identification and quantification of predominant metabolites of synthetic cannabinoid MAB-CHMINACA in an authentic human urine specimen. Drug Test Anal. doi:10.1002/dta.2220