Highly sensitive and selective detection of creatinine by combined use of MISPE and a complementary MIP-sensor

Guanidinoacetate methyltransferase deficiency is a recently discovered inborn defect of creatine biosynthesis which reduces serum creatinine concentrations to as low as 0.58 mu g mL(-1) (or 0.00058 mu g mL(-1) after 1,00o-fold dilution). To measure ultra trace levels of creatinine in diluted samples, molecularly imprinted solid-phase extraction (MISPE) and molecularly imprinted polymer (MIP) sensor techniques have been found to be inadequate. A combination of these techniques (i.e. MISPE hyphenated with use of an MIP-sensor), reported in this paper, has been found to be highly suitable for direct assay of creatinine in highly diluted human blood serum without complicated pretreatment of the sample. The proposed technique has the potential to enhance the sensitivity of creatinine measurement from mu g mL(-1) to ng mL(-1) in highly dilute aqueous samples in which the concentrations of interfering constituents are reduced to negligible levels. In this work the sensitivity to creatinine was found to be improved compared with that of the MIP-sensor method alone (limit of detection, LOD, 0.00149 mu g mL(-1)). After preconcentration by MISPE and use of the sensor the detection limit for creatinine was as low as 0.00003 mu g mL(-1) (RSD = 0.94%, S/N= 3; 50-fold preconcentration factor) in aqueous samples.