Commercially, creatinine is measured using one of two methods:
- Reaction with alkaline picric acid (Jaffe method)
- Enzymatically, using coupled reactions
The Jaffe method was originally developed in 1886 (Delanghe, 2011) and remains in use to date. In this method, creatinine reacts with alkaline picric acid, forming an orange/red complex that can be measured spectrophotometrically in a reaction that is kinetically monitored. However, the Jaffe reaction is not creatinine-specific, thus, manufacturers incorporate methods by which the assay conditions minimize background interference (Clarke, 2016). For example, metabolites such as bilirubin, glucose, and acetone may interfere with the assay, requiring background compensation techniques to be employed to minimize interference.
In routine outpatient populations, the risk of clinically significant assay interference is relatively low (Schmidt, 2015). However, some patient populations may need alternative methods to ensure reliable results (e.g., those with liver disease, newborns).