Metabolism of Carfentanil, an Ultra-Potent Opioid, in Human Liver Microsomes and Human Hepatocytes by High-Resolution Mass Spectrometry.

摘要: Carfentanil is an ultra-potent synthetic opioid. No human carfentanil metabolism data are available. Reportedly, Russian police forces used and remifentanil to resolve a hostage situation in Moscow 2002. This alleged use prompted interest the pharmacology toxicology of humans. Our study was conducted identify metabolites assess carfentanil’s metabolic clearance, which could contribute its acute toxicity We Simulations Plus’s ADMET Predictor™ Molecular Discovery’s MetaSite™ predict possible metabolite formation. Both programs gave similar results that were generally good but did not capture all seen vitro. incubated with hepatocytes for up 1 h analyzed samples on Sciex 3200 QTRAP mass spectrometer measure parent compound depletion extrapolated represent intrinsic clearance. Pooled primary then 6 identification 5600+ TripleTOF (QTOF) high-resolution spectrometer. MS MS/MS analyses elucidated structures most abundant metabolites. Twelve identified total. N-Dealkylation monohydroxylation piperidine ring dominant pathways. Two N-oxide one glucuronide observed. Surprisingly, ester hydrolysis major pathway carfentanil. While liver microsomal system demonstrated rapid clearance by CYP enzymes, hepatocyte incubations showed much slower possibly providing some insight into long duration effects.