Donor–acceptor covalent organic framework nanofilm-based laser desorption/ionization mass spectrometry for rapid and sensitive determination of creatinine in human serum

Creatinine (Cre), a metabolite generated by muscles and kidneys, holds significant importance in clinical screening and detection of kidney disease. However, the existing clinical detection of Cre, such as the Jaffe reaction-based colorimetric method, requires complex sample pretreatment and is subject to interference in biological samples. Herein, a surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) method based on a donor-acceptor covalent organic framework (D-A COF) nanofilm as a substrate was proposed for Cre determination in human serum. The D-A COF nanofilm was synthesized using a solvothermal reaction on indium-tin-oxide (ITO)-coated glass plates, which featured uniform surfaces, good thermal stability, and excellent UV absorption. Compared with conventional organic matrices, the D-A COF nanofilm-based LDI-MS method showed low background interference and high MS response and was successfully used for the analysis of low-weight molecules, such as amino acids, bisphenols, and estrogens. On this basis, the D-A COF nanofilm-based LDI-MS method was developed for the determination of Cre in human serum. This method showed good linearity in the range of 14.0-750.0 μmol L^-1 with a low limit of detection (LOD) of 4.5 μmol L^-1, making it suitable for the determination of Cre in human serum with different concentration levels. This work demonstrates the potential of this method for the clinical determination of Cre in human serum and provides a new direction for the screening and determination of other small-molecule clinical markers.