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<p>Methamphetamine is a potent central nervous system stimulant with a complex history ranging from widespread mid-twentieth-century medicinal and military use to its current status as a severely restricted, illicit drug. Despite its long history, direct experimental data regarding the ultra-long-term stability of methamphetamine in finished pharmaceutical dosage forms remain virtually non-existent. This study investigated the long-term stability of methamphetamine hydrochloride by analyzing authentic, nearly nine-decades-old samples of <i>Pervitin</i> manufactured in Germany in the late 1930s, representing the oldest surviving commercial methamphetamine samples in the world. Using an optimized RP-HPLC–UV method, the methamphetamine hydrochloride was quantified in two distinct matrices: solid oral tablets and liquid injectable ampoules. In the tablets, a content of 75% of the manufacturer’s declared value was found, whereas the liquid injectable solution exhibited a retained content of 95.3% of the manufacturer’s declared value. Capillary zone electrophoresis and ionic balance modeling confirmed that methamphetamine in the injectable formulation was exclusively present as a hydrochloride salt. Strikingly, HPLC–MS/MS provided pristine total ion chromatograms, confirming a complete absence of organic manufacturing impurities or ultra-long-term degradation products. These findings provide definitive proof of the exceptional chemical stability of methamphetamine hydrochloride over nearly a century and suggest that the lower active content observed in the tablets is firmly attributable to technical problems at the time of formulation manufacturing.</p> Graphical Abstract <p></p>

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Chemical archaeology of methamphetamine: analysis of the nearly nine-decades-untouched historical Pervitin formulations

  • 期刊论文

  • 发表日期：

    2026年8月2日

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  • Karel Nesměrák,
  • Lukáš Janeček,
  • Tomáš Křížek,
  • Tomáš Lener,
  • Ladislav Svatoš,
  • Martin Štícha

摘要

Methamphetamine is a potent central nervous system stimulant with a complex history ranging from widespread mid-twentieth-century medicinal and military use to its current status as a severely restricted, illicit drug. Despite its long history, direct experimental data regarding the ultra-long-term stability of methamphetamine in finished pharmaceutical dosage forms remain virtually non-existent. This study investigated the long-term stability of methamphetamine hydrochloride by analyzing authentic, nearly nine-decades-old samples of Pervitin manufactured in Germany in the late 1930s, representing the oldest surviving commercial methamphetamine samples in the world. Using an optimized RP-HPLC–UV method, the methamphetamine hydrochloride was quantified in two distinct matrices: solid oral tablets and liquid injectable ampoules. In the tablets, a content of 75% of the manufacturer’s declared value was found, whereas the liquid injectable solution exhibited a retained content of 95.3% of the manufacturer’s declared value. Capillary zone electrophoresis and ionic balance modeling confirmed that methamphetamine in the injectable formulation was exclusively present as a hydrochloride salt. Strikingly, HPLC–MS/MS provided pristine total ion chromatograms, confirming a complete absence of organic manufacturing impurities or ultra-long-term degradation products. These findings provide definitive proof of the exceptional chemical stability of methamphetamine hydrochloride over nearly a century and suggest that the lower active content observed in the tablets is firmly attributable to technical problems at the time of formulation manufacturing.

Graphical Abstract