ABSTRACT
Accurate quantification of creatinine (Cre) is important to estimate glomerular filtration rate (GFR). Differences among various methods of Cre quantification were previously noted. This study aims to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for serum Cre and compare this method with clinical routine methods. LC-MS/MS analysis was performed on API 4000 triple quadrupole mass spectrometer coupled with an Agilent 1200 liquid chromatography system. After adding isotope-labeled Cre-d3 as internal standard, serum samples were prepared via a one-step protein precipitation with methanol. The LC-MS/MS method was compared with frequently used enzymatic method and Jaffe method. This developed method, with a total run time of 3 min, had a lower limit of quantification of 4.4 µmol/L, a total imprecision of 1.15%-3.84%, and an average bias of 1.06%. No significant matrix effect, carryover, and interference were observed for the LC-MS/MS method. The reference intervals of serum Cre measured by LC-MS/MS assay were 41-79 µmol/L for adult women, and 46-101 µmol/L for adult men. Using LC-MS/MS as a reference, the enzymatic method showed an average bias of -2.1% and the Jaffe method showed a substantial average bias of 11.7%. Compared with the LC-MS/MS method, significant negative bias was observed for the enzymatic and Jaffe methods in hemolytic and lipimic samples. We developed a simple, specific, and accurate LC-MS/MS method to analyze serum Cre. Discordance existed among different methods.
