Biodegradability and transformation of human pharmaceutical active ingredients in environmentally relevant test systems

Human pharmaceutical active ingredients that are orally or parenterally administered may be metabolised in the body and after excretion may be further transformed in the receiving environmental compartments. The optimal outcome from an environmental point of view—complete mineralisation—is rarely observed. Small molecule pharmaceuticals are commonly not readily biodegradable according to Organisation for Economic Cooperation and Development (OECD) 301 tests. However, primary transformation is often observed. To gain information on the transformation of active ingredients in the environment, long-term studies like transformation in aquatic water/sediment systems according to OECD guideline 308 are required for the environmental risk assessment for human active pharmaceutical ingredients. Studies received until mid 2010 as part of the dossiers for marketing authorisation applications were evaluated concerning transformation products. The evaluation revealed that in 70 % of the studies, at least one transformation product (TP) is formed above 10 % of the originally applied dose, but in only 26 % of the studies are all TP identified. The evaluation also revealed that some TP of pharmaceutical active ingredients show a considerably longer DT(50) compared to the parent compound. An example is the TP (val)sartan acid that is formed from an antihypertensive compound.