A simplified, rapid LC-MS/MS assay for serum and salivary creatinine

In routine clinical laboratories, serum creatinine is typically measured on automated analyzers using colorimetric or enzymatic assays, which are both susceptible to interferences that can lead to incorrect measurement. Here, we present a straightforward and rapid LC-MS/MS assay for serum creatinine using methanol extraction, with separation performed using a strong cation exchange column. Results from this newly developed method were compared against those from an automated Abbott Architect kinetic Jaffe method. We also assessed the effect of bilirubin and glucose, as interferants, on both methods. Our LC-MS/MS assay has a run time of 1.1 min, uses a relatively small sample volume of 10 µL and has a within-batch imprecision of 1.1-1.8% at the concentrations tested, which is within the range necessary for routine clinical use. Recovery from serum samples spiked with creatinine was >95%, and glucose and bilirubin were not found to interfere in the assay. Glucose was observed to significantly interfere in the kinetic Jaffe method, while bilirubin had a variable effect. We also determined that creatinine can be measured from saliva using our method, and that salivary concentrations are, on average, 15% of those in serum. This assay provides an alternative for patient sample analysis where interference is expected in routine creatinine methods.