Temozolomide (TMZ) was FDA approved for treatment of glioblastoma (GBM) in 1995 and is a life-extending (and sometimes life-saving¹) drug for GBM and other cancers.² TMZ has been administered to thousands of patients and has been shipped around the world for over three decades; patients typically ingest grams of TMZ during a standard treatment regimen.³ We recently reported the use of TMZ as a reagent for the synthesis of methyl esters and cyclopropanes with many benefits (including safety and convenience) compared to diazomethane.⁴ Our paper utilized TMZ under aqueous conditions at temperatures up to 60 °C, well under the decomposition point for the solid material.⁵

A recent manuscript from Sperry and co-workers⁶ showed that under more forcing conditions TMZ has the potential to be hazardous. After defining a decomposition point in the 170–180 °C range via differential scanning calorimetry, the authors performed impact testing by dropping a 10 kg weight on solid TMZ. Although no flame was produced, smoke was observed during this testing. A series of other detailed experiments are reported in this manuscript, including heating solid TMZ at 75 °C for two days, a friction sensitivity test, and the burning of a 100 gram sample of TMZ in a fire of kerosene-soaked sawdust; no explosions occurred in any of these tests. However, ignition of TMZ under confinement did lead to the production of excess pressure.

Our laboratory has not experienced any safety incidents during our extensive use of TMZ and reports of explosive episodes are absent from the literature, despite nearly four decades of chemical and biological research, distinguishing it from diazomethane. Sperry and co-workers have further defined the conditions for safely working with TMZ, and caution is warranted when working with this reagent especially under the elevated pressures or temperatures mentioned above.

替莫唑胺 (TMZ) 于 1995 年被 FDA 批准用于治疗胶质母细胞瘤 (GBM)，是一种用于 GBM 和其他癌症的延长生命（有时是挽救生命¹）的药物。² TMZ 已用于数千名患者，并已运往世界各地超过三十年；患者通常在标准治疗方案期间摄入 TMZ 克数。³我们最近报道了使用 TMZ 作为合成甲酯和环丙烷的试剂，与重氮甲烷相比具有许多优点（包括安全性和便利性）。⁴我们的论文在温度高达 60 °C 的水性条件下使用 TMZ，远低于固体材料的分解点。⁵

Sperry 和同事⁶最近的一份手稿表明，在更强迫的条件下，TMZ 有潜在危险。在通过差示扫描量热法定义 170–180 °C 范围内的分解点后，作者通过在固体 TMZ 上落下 10 公斤重物进行了冲击测试。尽管没有产生火焰，但在该测试期间观察到烟雾。本手稿还报道了一系列其他详细实验，包括在 75 °C 下加热固体 TMZ 两天、摩擦敏感性测试以及在煤油浸泡的锯末的火中燃烧 100 克 TMZ 样品；在任何这些测试中都没有发生爆炸。然而，在限制条件下点燃 TMZ 确实会导致产生过压。

我们的实验室在广泛使用 TMZ 期间没有发生任何安全事故，尽管进行了近四年的化学和生物研究，将其与重氮甲烷区分开来，但文献中没有关于爆炸事件的报告。Sperry 和同事进一步定义了安全使用 TMZ 的条件，在使用该试剂时必须小心，尤其是在上述升高的压力或温度下。