So I have done some thinking on this subject and done a little kitchen experimentation with levamisole. I want to state up front that there are two references that are relevant but I don’t have access to:
1) N. A. Dickinson, H. E. Hudson and P. J. Taylor, "Levamisole: its stability in aqueous solutions at elevated temperatures. Part I. Isolation and identification of decomposition products formed in aqueous solutions of levamisole stored under nitrogen and oxygen at 100 °C" Analyst, 1971, 96, 235-243
2) V. Das Gupta, "Stability of cocaine hydrochloride solutions at various pH values as determined by high-pressure liquid chromatography", International Journal of Pharmaceutics , vol. 10, 1982, pp. 249 -257.
If it’s within the forum rules, perhaps someone with access could post copies here. That said, here goes:
About 0.75 g of levamisole HCl was dissolved in about ~50 mL of water in a small glass bottle. About 0.5 g (about 100% molar excess) of NaHC03 was added and allowed to dissolve. The solution was shaken vigorously over several minutes with evolution of gas, CO2 most likely, and a faint precipitate. The sample at this point had a slight but unmistakable smell of a free base amine.
The bottle was microwaved until the solution came to a boil (about 20 seconds) and removed from the microwave. The sample now had an unmistakable, unpleasant smell of a thiol, very much like the smell of leaking natural gas. Yuck. On cooling a noticeable white precipitate formed. The mixture was extracted 2 x with ~10 mL an organic solvent and the solvent dried and allowed to evaporate on a watch glass, leaving a small amount of a clear oily liquid with a strong thiol-like smell. (I’m thinking this liquid product is probably described in reference 1 above. Also relevant is this DEA link:
http://www.justice.gov/dea/programs/forensicsci/microgram/journal_v6_num34/pg3.html.)
The oily liquid is insoluble in water, easily soluble in 0.1 M aqueous NaOH (pH 13) and only partially soluble in aqueous NaOH at pH 11.5.
It is known that thoils are fairly acidic, with aliphatic thiols having pKa in the 10.5 range. This would explain why this oily liquid is soluble at pH 13, existing almost completely as the conjugate base, a thoilate ion. However, it is also known that cocaine decomposes (ester hydrolysis) over time in neutral to basic solutions, with the rate of decomposition dependent on several factors including pH and temperature.
So the idea is that if cocaine can withstand several minutes in pH 13 solution with acceptable losses, then we may have a simple way to remove the levamisole. On the other hand, if the cocaine decomposes too quickly at this pH, then such an approach would obviously not be acceptable. My guess is that hydrolysis is fairly rapid at this pH, but I was hoping to hear from others here who may know more about this.
