Questioning European policy on alkyl mesylate impurities

Creating policies on scientific and medical issues is not an easy task. Often, decisions must be made when scientific knowledge is uncertain, and so a policy may be based on false hypotheses. Ideally, any dubious hypothesis is disproved by emerging evidence, but situations can occur where institutional inertia and dogma allow the policy to remain in place. An example of this can be seen in the suggestion that sulfonic acid salt drugs may be unsafe.

Over half of the top prescription drugs are presented as salts in order to optimise their pharmaceutical properties. Sulfonic acid salts such as mesylate (methanesulfonate) often provide the best technical solution, although hypothetical safety concerns were raised nearly 20 years ago.

In late 2000, the European Department for the Quality of Medicines (EDQM), secretariat to the European Pharmacopoeia, suggested that an ester-forming side-reaction could occur during the synthesis of a mesylate salt by addition of methanesulfonic acid to a pharmaceutical base dissolved in an alcoholic solvent such as ethanol. Thus, a toxic alkyl mesylate (ethyl methanesulfonate; EMS) might be present as an impurity in the mesylate-salt drug substance.