Producing the most likely impurities of a Given Product for Use in Developing a Powerful Analytical Method

In order to develop a good purity analysis for an organic substance one needs to have some method to assess different methods. The better the method separates and quantifies more impurities from the product. A better method the more impurities it separates and the greater the degree of separation between the closest impurity and the product without losing some degree of separation for any single impurity. A better method separates distinctly even an impurity designed to have a very minor difference from the product. Is there a way to prepare a product sample with larger amounts of the most likely potential impurities?

There are two classes of impurities. Impurities that are product degradation derived; that is, they come from the desired product and arise from reactions upon the desired product after it has been isolated and purified. A different class of impurities are formed at the time of the synthesis of the desired product and which were not completely removed by the isolation and purification process performed before packaging of final product. These impurities are process characteristic. It is this second type that are considered here. These impurities are produced in greater or lesser amounts by variation in the continuous variables controlling the process.

A third group of impurities are created by changing the discontinuous variables of the process step, such as reagents, reagent purity, solvent, solvent purity, substrate purity, processing chemicals When the discontinuous variables are not altered this set of impurities do not appear and do not need to be further mentioned herein.

Temperature is the most significant continuous variable and it can produce the most substantial changes in chemical reactivity. If we are seeking a complete reaction it is likely that the transformation is self terminating and will essentially stop when the correct time has expired with very little occurring after this required reaction time. Increasing the temperature by 10 C according to a rule of thumb will double the rate of reaction. This will also allow competing reactions which are limited under the more preferred conditions to compete and produce by-products.

Thus an increase in the temperatures of each of the different stages of the reaction by 10 C and a decrease in the time by half in each stage should produce more impurities in the final product and these impurities should reflect realistic possible impurities.   If possible the extent of disappearance of starting material should be kept about the same.