Optimization and application of octadecyl-modified monolithic silica for solid-phase extraction of drugs in whole blood samples

•Monolithic silica prepared for optimal extraction of analytes in whole blood.•Concentrated analytes in monolithic silica eluted using small volume of the solvent.•High-throughput extraction achieved without using evaporation.

Monolithic silica in MonoSpin for solid-phase extraction of drugs from whole blood samples was developed to facilitate high-throughput analysis. Monolithic silica of various pore sizes and octadecyl contents were synthesized, and their effects on recovery rates were evaluated. The silica monolith M18-200 (20 μm through-pore size, 10.4 nm mesopore size, and 17.3% carbon content) achieved the best recovery of the target analytes in whole blood samples. The extraction proceeded with centrifugal force at 1000 rpm for 2 min, and the eluate was directly injected into the liquid chromatography-mass spectrometry system without any tedious steps such as evaporation of extraction solvents. Under the optimized condition, low detection limits of 0.5-2.0 ng mL−1 and calibration ranges up to 1000 ng mL−1 were obtained. The recoveries of the target drugs in the whole blood were 76-108% with relative standard deviation of less than 14.3%. These results indicate that the developed method based on monolithic silica is convenient, highly efficient, and applicable for detecting drugs in whole blood samples.