Do any pharmaceuticals increase in potency or toxicity over time?

Pursuing a question raised in [these comments](https://chemistry.stackexchange.com/a/6379/5354):


**Are there any known pharmaceuticals that increase in potency or toxicity during storage, or over periods of months to years?**


If not, what if we broaden the question to include any bioactive chemical?


My hypothesis is that the answer is **no** due to the following considerations:


1. If we limit the scope to pharmaceuticals we often find that the bioactive components of a chemical are specific isomers. In that case other isomers are relatively inert. Over time racemization can only *decrease* the concentration of the bioactive isomers,\* so under this mechanism potency can only decrease with time. (I can't find any examples in which non-therapeutic isomers are more toxic than the therapeutic isomers.)
2. The other mechanisms of chemical change that I can think of chemically affecting a bioactive substance during extended storage are heat, light, evaporation, and atmospheric oxidation and moisture. We might rule out all of these but heat in the case of *properly* stored pharmaceuticals, which are formulated and/or packaged to prevent exposure to these influences. But even if we allow for exposure to any or all of these (keeping heat within reason – say under 60°C) I can't think of any examples by which these processes increase toxicity of any chemical.


Any specific examples or general suggestions to the contrary are welcome!




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\* Silas W. Smith, [Chiral Toxicology: It's the Same Thing…Only Different](https://academic.oup.com/toxsci/article/110/1/4/1668162), Toxicological Sciences, Volume 110, Issue 1, July 2009, Pages 4–30, <https://doi.org/10.1093/toxsci/kfp097>
provides an extensive survey of this question. I certainly could have missed something during reading, but it does state early on that in drugs offered only as enantiomers "...the other isomer has no clinical effect or adverse effects *in vivo*." Some examples show that while "adverse" effects (which I'll classify under "toxicity") can be found in non-therapeutic isomers, they do not exceed the adverse effects found in the therapeutic isomer. So in the worst case it appears that a pharmaceutical can lose potency but not toxicity over time due to racemization, but this does not constitute an *increase* in "toxicity."


