Construction of a two-dimensional magnetic solid phase extraction microfluidic chip/tandem mass spectrometry platform for the determination of cytarabine in plasma

A novel concept of two-dimensional magnetic solid phase extraction microfluidic chip (2D-MSPE-chip) was proposed, in which two or even more different separation mechanisms of solid phase extraction units were designed and constructed on microfluidic chips in series. The synthesized Fe 3 O 4 -UiO-66-C18 was used in the first dimension to retain protein and phospholipid through hydrophobic effect and Zr O P coordination, which could almost eliminate the interference of the matrix effect on the mass spectrum. The second dimensional material utilized Fe 3 O 4 -UiO-66-NH 2 to enable cytarabine enrichment via π–π and hydrogen bonding. The parameters of 2D MSPE-Chip/tandem MS method such as desorption solvent (5 % acetic acid acetonitrile), loading solvent (20 % acetonitrile), and flow rate for extraction and desorption (10 μL/min) were select. The LOD of the established method for cytarabine in plasma was 0.13 ng/mL, and the linear range was between 2.0 ng/mL and 1000 ng/mL with correlation coefficient (R 2  = 0.9991). The matrix effect was −5.0 %. The recovery rate of real samples ranged from 95.5 % to 104.8 %, with RSD ≤ 5.2 %. The chip design was simple and efficient and could be reused, thereby decreasing analysis expenses. It held considerable potential for application in rapid clinical diagnostics and precision medicine.