In order to develop a good purity analysis for an organic substance, one needs to have some method to assess different methods. A better method separates and quantifies more impurities from the product. A better method increases the degree of separation between the closest impurity and the product without losing separation for any other impurity. A better method separates more cleanly an impurity designed to have a very minor structural difference from the product.
But is there a way to prepare a resolution standard with larger amounts of the most likely potential impurities of the product? This becomes an important practical matter.
There are two types of impurities. Impurities that are derived from product degradation; that is, they come via the desired product and arise from reactions of the desired product occurring after it has been isolated and purified. A separate type of impurity is one that is formed at the time of the synthesis of the desired product and which is not completely removed by the isolation, separation, and purification processes performed before packaging the final product. Such impurities are characteristic of the process.
It is this second type that is considered here. These impurities are produced in greater or lesser amounts by variations from the proper continuous variables controlling the process.
New previously unobserved impurities are usually created by changing the discontinuous variables of the process step, such as reagents, reagent purity, reagent/substrate ratio, solvent, solvent purity, substrate purity, processing chemicals…
The most significant continuous variables are time and temperature.
The one that can produce the most profound or substantial changes in chemical reactivity is temperature. The effect of time is usually more limited because 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 relatively less occurring after this required reaction time. Increasing the temperature by 10 C according to a rule of thumb should double the rate of reaction. This will also allow competing reactions that are limited under the most preferred conditions to compete and produce by-products.
Thus, an increase in the temperatures of each of the different stages of the reaction by 10C 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.
Product separated from a process step stressed in this way should show increased amounts of the most likely process impurities.
If it does not, this is important information for your determination of critical parameters that you will need to work on at some point. Tests that provide a resolution standard go hand-in-hand with examining critical parameters!