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Purpose <p>Methamphetamine (MA) is widely abused worldwide and has long been a major social concern. To provide basic information for comparing MA toxicokinetics in humans, we analyzed changes in the serum and urinary concentrations of MA and its metabolites in mice and compared the toxicokinetic profiles at the toxic dose with those at the therapeutic dose.</p> Methods <p>Mice were administered therapeutic (1.5&#xa0;mg/kg) or toxic (15&#xa0;mg/kg) doses and blood and urine samples were collected. The serum concentrations of MA and its metabolite amphetamine (AMP), as well as the urinary concentrations of MA and its metabolites—AMP, <i>p</i>-hydroxymethamphetamine (OHMA), <i>p</i>-hydroxyamphetamine (OHAMP), and norephedrine (NEP) —were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p> Results <p>The serum AUC<sub>0–24</sub> values for MA and AMP were approximately 16 and 41 times higher, respectively, in the toxic dose group than those in the therapeutic dose group. The urinary AMP and OHAMP excretion levels were approximately 3.6 and 2.2 times higher, respectively, in the toxic dose group. The urinary [AMP] / [MA] ratio at all collected points and [AMP] / [OHMA] ratio in the 0–24&#xa0;h sample were significantly higher in the toxic than in the therapeutic dose group.</p> Conclusions <p>The results obtained from this study suggest that the metabolism of AMP to OHAMP and NEP was saturated during intoxication. Furthermore, the determination of whether a toxic dose had been administered within 24&#xa0;h or after 24&#xa0;h would be possible through a joint evaluation of the urinary [AMP] / [MA] and [AMP] / [OHMA] ratios.</p>

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Comparative analysis of toxicokinetic profiles of methamphetamine and its metabolites at toxic and therapeutic doses in mice

  • 期刊论文

  • 发表日期：

    2025年12月15日

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  • Misato Ishida,
  • Asuka Kaizaki-Mitsumoto,
  • Satoshi Numazawa

摘要

Purpose

Methamphetamine (MA) is widely abused worldwide and has long been a major social concern. To provide basic information for comparing MA toxicokinetics in humans, we analyzed changes in the serum and urinary concentrations of MA and its metabolites in mice and compared the toxicokinetic profiles at the toxic dose with those at the therapeutic dose.

Methods

Mice were administered therapeutic (1.5 mg/kg) or toxic (15 mg/kg) doses and blood and urine samples were collected. The serum concentrations of MA and its metabolite amphetamine (AMP), as well as the urinary concentrations of MA and its metabolites—AMP, p-hydroxymethamphetamine (OHMA), p-hydroxyamphetamine (OHAMP), and norephedrine (NEP) —were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results

The serum AUC0–24 values for MA and AMP were approximately 16 and 41 times higher, respectively, in the toxic dose group than those in the therapeutic dose group. The urinary AMP and OHAMP excretion levels were approximately 3.6 and 2.2 times higher, respectively, in the toxic dose group. The urinary [AMP] / [MA] ratio at all collected points and [AMP] / [OHMA] ratio in the 0–24 h sample were significantly higher in the toxic than in the therapeutic dose group.

Conclusions

The results obtained from this study suggest that the metabolism of AMP to OHAMP and NEP was saturated during intoxication. Furthermore, the determination of whether a toxic dose had been administered within 24 h or after 24 h would be possible through a joint evaluation of the urinary [AMP] / [MA] and [AMP] / [OHMA] ratios.