From the dosage form to the testing environment, water is used in almost every stage of drug formulation. Because of this, water problems can be a barrier to the formulation stage of drug development and can prevent progression to FDA approval.
HPLC: It’s all in the water
High-performance liquid chromatography (HPLC) is used to identify the exact composition of a drug, provide quantitative results, and monitor progression of a new therapeutic—but it requires very high-quality water. HPLC-grade water is ultrapure and has low conductivity and UV absorbance. It’s often provided and stored in sealed, solvent-rinsed containers to further avoid the possibility of contamination.
Different water contaminants have different effects on the reaction. For example, organic contamination can result in loss of resolution, contribute to ghost peaks, or cause retention time shifts and peak tailing. Ionic contaminants can reduce signal or increase adduct formation. These types of problems make results difficult to interpret and impossible to use for drug justification.
To mimic gastrointestinal conditions, you need very pure water
Some drug candidates, such as those used to treat inflammatory conditions, need to be tested under conditions that mimic an impaired gastrointestinal environment. This is because some medications can cause altered physiology, such as tissue toxicity or intestinal microbiome problems, as a side effect. As part of the drug development process, clinical researchers may dissolve existing pharmaceuticals in aqueous buffers to create representative environments that mimic known GI tract impairments. These environments require very pure water so that the research team knows exactly what is being delivered to the site.