Strategies to distinguish new synthetic cannabinoid FUBIMINA (BIM-2201) intake from its isomer THJ-2201: metabolism of FUBIMINA in human hepatocytes

Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA (2014) Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend 144:12–41 Patton AL, Seely KA, Chimalakonda KC, Tran JP, Trass M, Miranda A, Fantegrossi WE, Kennedy PD, Dobrowolski P, Radominska-Pandya A, McCain KR, James LP, Endres GW, Moran JH (2013) Targeted metabolomic approach for assessing human synthetic cannabinoid exposure and pharmacology. Anal Chem 85:9390–9399 Wiley JL, Marusich JA, Lefever TW, Antonazzo KR, Wallgren MT, Cortes RA, Patel PR, Grabenauer M, Moore KN, Thomas BF (2015) AB-CHMINACA, AB-PINACA, and FUBIMINA: affinity and potency of novel synthetic cannabinoids in producing Δ9-tetrahydrocannabinol-like effects in mice. J Pharmacol Exp Ther 354:328–339 Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S (2016) A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol 54:1–13 Wilkinson SM, Banister SD, Kassiou M (2015) Bioisosteric fluorine in the clandestine design of synthetic cannabinoids. Aust J Chem 68:4–8 Hermanns-Clausen M, Kneisel S, Szabo B, Auwärter V (2013) Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 108:534–544 Seely KA, Lapoint J, Moran JH, Fattore L (2012) Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiat 39:234–243 Shanks KG, Winston D, Heidingsfelder J, Behonick G (2015) Case reports of synthetic cannabinoid XLR-11 associated fatalities. Forensic Sci Int 252:e6–e9 Tse R, Kodur S, Squires B, Collins N (2014) Sudden cardiac death complicating acute myocardial infarction following synthetic cannabinoid use. Intern Med J 44:934–936 Uchiyama N, Shimokawa Y, Kikura-Hanajiri R, Demizu Y, Goda Y, Hakamatsuka T (2015) A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products. Forensic Toxicol 33:244–259 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 32:105–115 DeRuiter J, Smith FT, Abdel-Hay K, Clark CR (2014) Analytical differentiation of 1-alkyl-3-acylindoles and 1-acyl-3-alkylindoles: isomeric synthetic cannabinoids. Anal Chem 86:3801–3808 Scheidweiler KB, Jarvis MJ, Huestis MA (2015) Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry. Anal Bioanal Chem 407:883–897 Diao X, Scheidweiler KB, Wohlfarth A, Pang S, Kronstrand R, Huestis MA (2016) In vitro and in vivo human metabolism of synthetic cannabinoids FDU-PB-22 and FUB-PB-22. AAPS J 18:455–464 Diao X, Wohlfarth A, Pang S, Scheidweiler KB, Huestis MA (2016) High-resolution mass spectrometry for characterizing the metabolism of synthetic cannabinoid THJ-018 and its 5-fluoro analog THJ-2201 after incubation in human hepatocytes. Clin Chem 62:157–169 Wen B, Zhu M (2015) Applications of mass spectrometry in drug metabolism: 50 years of progress. Drug Metab Rev 47:71–87 Gao R, Li L, Xie C, Diao X, Zhong D, Chen X (2012) Metabolism and pharmacokinetics of morinidazole in humans: identification of diastereoisomeric morpholine N +-glucuronides catalyzed by UDP glucuronosyltransferase 1A9. Drug Metab Dispos 40:556–567 Diao X, Deng P, Xie C, Li X, Zhong D, Zhang Y, Chen X (2013) Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role of cytochrome P450s and alcohol dehydrogenase in biotransformation. Drug Metab Dispos 41:430–444 Zhu M, Ma L, Zhang H, Humphreys WG (2007) Detection and structural characterization of glutathione-trapped reactive metabolites using liquid chromatography-high-resolution mass spectrometry and mass defect filtering. Anal Chem 79:8333–8341 Soars MG, McGinnity DF, Grime K, Riley RJ (2007) The pivotal role of hepatocytes in drug discovery. Chem Biol Interact 168:2–15 Baranczewski P, Stanczak A, Sundberg K, Svensson R, Wallin A, Jansson J, Garberg P, Postlind H (2006) Introduction to in vitro estimation of metabolic stability and drug interactions of new chemical entities in drug discovery and development. Pharmacol Rep 58:453–472 Diao X, Pang X, Xie C, Guo Z, Zhong D, Chen X (2014) Bioactivation of 3-n-butylphthalide via sulfation of its major metabolite 3-hydroxy-NBP: mediated mainly by sulfotransferase 1A1. Drug Metab Dispos 42:774–781 Wohlfarth A, Castaneto MS, Zhu M, Pang S, Scheidweiler KB, Kronstrand R, Huestis MA (2015) Pentylindole/pentylindazole synthetic cannabinoids and their 5-fluoro analogs produce different primary metabolites: metabolite profiling for AB-PINACA and 5F-AB-PINACA. AAPS J 17:660–677 Castaneto MS, Wohlfarth A, Pang S, Zhu M, Scheidweiler KB, Kronstrand R, Huestis MA (2015) Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry. Forensic Toxicol 33:295–310 Ellefsen KN, Wohlfarth A, Swortwood MJ, Diao X, Concheiro M, Huestis MA (2016) 4-Methoxy-α-PVP: in silico prediction, metabolic stability, and metabolite identification by human hepatocyte incubation and high-resolution mass spectrometry. Forensic Toxicol 34:61–75 Swortwood MJ, Carlier J, Ellefsen KN, Wohlfarth A, Diao X, Concheiro-Guisan M, Kronstrand R, Huestis MA (2016) In vitro, in vivo and in silico metabolic profiling of α-pyrrolidinopentiothiophenone, a novel thiophene stimulant. Bioanalysis 8:65–82 McNaney CA, Drexler DM, Hnatyshyn SY, Zvyaga TA, Knipe JO, Belcastro JV, Sanders M (2008) An automated liquid chromatography-mass spectrometry process to determine metabolic stability half-life and intrinsic clearance of drug candidates by substrate depletion. Assay Drug Dev Technol 6:121–129 Diao XX, Zhong K, Li XL, Zhong DF, Chen XY (2015) Isomer-selective distribution of 3-n-butylphthalide (NBP) hydroxylated metabolites, 3-hydroxy-NBP and 10-hydroxy-NBP, across the rat blood-brain barrier. Acta Pharmacol Sin 36:1520–1527 Obach RS (1999) Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: an examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab Dispos 27:1350–1359 Lave T, Dupin S, Schmitt C, Valles B, Ubeaud G, Chou RC, Jaeck D, Coassolo P (1997) The use of human hepatocytes to select compounds based on their expected hepatic extraction ratios in humans. Pharmaceut Res 14:152–155 Zhong S, Jones R, Lu W, Schadt S, Ottaviani G (2015) A new rapid in vitro assay for assessing reactivity of acyl glucuronides. Drug Metab Dispos 43:1711–1717 Uldam HK, Juhl M, Pedersen H, Dalgaard L (2011) Biosynthesis and identification of an N-oxide/N-glucuronide metabolite and first synthesis of an N-O-glucuronide metabolite of Lu AA21004. Drug Metab Dispos 39:2264–2274 Ibrahim H, Couderc F, Perio P, Collin F, Nepveu F (2013) Behavior of N-oxide derivatives in atmospheric pressure ionization mass spectrometry. Rapid Commun Mass Spectrom 27:621–628 Ismail IM, Dear GJ, Roberts AD, Plumb RS, Ayrtont J, Sweatman BC, Bowers GD (2002) N-O glucuronidation: a major human metabolic pathway in the elimination of two novel anti-convulsant drug candidates. Xenobiotica 32:29–43 Freijo TD Jr, Harris SE, Kala SV (2014) A rapid quantitative method for the analysis of synthetic cannabinoids by liquid chromatography-tandem mass spectrometry. J Anal Toxicol 38:466–478 Skopp G, Potsch L (2002) Stability of 11-nor-Δ9-carboxy-tetrahydrocannabinol glucuronide in plasma and urine assessed by liquid chromatography-tandem mass spectrometry. Clin Chem 48:301–306 Scheidweiler KB, Schwope DM, Karschner EL, Desrosiers NA, Gorelick DA, Huestis MA (2013) In vitro stability of free and glucuronidated cannabinoids in blood and plasma following controlled smoked cannabis. Clin Chem 59:1108–1117 Li XD, Xia SQ, Lv Y, He P, Han J, Wu MC (2004) Conjugation metabolism of acetaminophen and bilirubin in extrahepatic tissues of rats. Life Sci 74:1307–1315 Gao C, Zhang H, Guo Z, You T, Chen X, Zhong D (2012) Mechanistic studies on the absorption and disposition of scutellarin in humans: selective OATP2B1-mediated hepatic uptake is a likely key determinant for its unique pharmacokinetic characteristics. Drug Metab Dispos 40:2009–2020 Xie C, Zhou J, Guo Z, Diao X, Gao Z, Zhong D, Jiang H, Zhang L, Chen X (2013) Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol 168:1687–1706