A study of the metabolism of methamphetamine and 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in isolated rat hepatocytes.
T Kanamori, K Tsujikawa, Y Ohmae, Y T Iwata, H Inoue, T Kishi, T Nakahama, Y Inouye
Forensic science international March 10, 2005 DOI: 10.1016/j.forsciint.2004.04.084 via PubMed
Summary
AI-generated from the abstractThe metabolism of methamphetamine (MA) and 4-bromo-2,5-dimethoxyphenethylamine (2C-B) was examined in freshly isolated rat hepatocytes and compared with in vivo results. For MA, the major metabolite was p-hydroxymethamphetamine, matching the urinary excretion profile in rats fed MA. For 2C-B, the major metabolites were 2-O-desmethyl-2C-B and a carboxylic acid derivative, a slight deviation from in vivo findings where 5-O-desmethyl-N-acetyl-2C-B predominated. Metabolites with a hydroxy group were largely conjugated, except for 2-O-desmethyl-2C-B. The primary hepatocyte culture system shows potential as a quick method for estimating the in vivo metabolic fate of abused drugs.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Freshly isolated rat hepatocytes from male Wistar rats |
| Interventions | Methamphetamine 4-bromo-2 5-dimethoxyphenethylamine (2C-B) |
| Key finding | The major metabolite of methamphetamine in rat hepatocytes was p-hydroxymethamphetamine, matching in vivo results, while for 2C-B the major metabolites were 2-O-desmethyl-2C-B and a carboxylic acid derivative, slightly deviating from in vivo findings. |
Abstract
The metabolism of methamphetamine (MA) and 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in freshly isolated rat hepatocytes was investigated, and compared with in vivo results. A suspended hepatocyte culture, established from male Wistar rats using a collagenase perfusion technique, was incubated in the presence of MA or 2C-B. After enzymatic hydrolysis of the conjugated forms, the metabolites were extracted by liquid-liquid partition and analyzed by gas chromatography/mass spectrometry (GC/MS). Amphetamine, p-hydroxymethamphetamine and p-hydroxyamphetamine were detected in the culture fluids of the rat hepatocytes inoculated with MA. The alcohol derivative, carboxylic acid derivative, 2-O-desmethyl-2C-B, 2-O-desmethyl-N-acetyl-2C-B and 5-O-desmethyl-N-acetyl-2C-B were detected in the case of 2C-B. The major metabolite of MA in rat hepatocytes was p-hydroxymethamphetamine. This is in good agreement with the urinary excretion profile for rats that were fed MA. 2-O-Desmethyl-2C-B and the carboxylic acid derivative were the major recovered metabolites of 2C-B in the rat hepatocyte culture, a slight deviation from the in vivo findings, in which 5-O-desmethyl-N-acetyl-2C-B was found to be the main component. Metabolites with a hydroxy group were largely present in their conjugated forms in the culture fluids, except for 2-O-desmethyl-2C-B. Taking these results into consideration, a primary hepatocyte culture system has the potential to provide a quick and handy method for estimating the in vivo metabolic fate of abused drugs.