Raw materials intermediates, DS, excipients

The impurities contained in the solvents could have several effects on the raw materials  

Due to the potential concentration of these impurities, they should be tested for in both DS and excipients and even in intermediates of synthesis if the latter constitute the penultimate stepofthe synthesis and if solvents belong to class 1 or class 2 solvent (see Chapter 16.2). 

This case has already been illustrated (see paragraph 14.21.1.2.1.6.5). The skills of the chemist together with those of the analyst are needed to ensure that the presence of unexpected impurities can be detected. By way of example, the reactions involving the keto-enol tautomerism deserve to be mentioned. The equilibrium is very sensitive to the solvent so that the presence of other solvents as impurities in the main solvent can modify the keto-enol ratio leading to irreproducibility in the chemical process. 

Some solvents, as mentioned in the paragraph 14.21.1.2.1.5, can contain very active entities such as aldehydes and peroxides. For example, if the raw material contains primary or sec- 

This issue is may be less known except for chemists working in this specialized area. Because the consequences can be important for the processability, stability and occasionally bioavailability of the drug substance in its formulation, it is relevant to comment on this subject. 

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