Silylation is a powerful derivatization technique used popularly in GC/MS analysis due to the high affinity with oxygen, and enhancement of sensitivity and chromatographic behavior. But, since the hydrolysis vulnerability of silyl derivatives, the application of silyl derivatization to LC-ESI/MS analysis is challenging. Herein, we describe the availability of silyl derivatization in LC-ESI/MS and its effect on ionization efficiency and chromatographic behavior.

As results, we discovered a hydrolysis-resistant silyl reagent with specific moiety on silicon. The silyl derivatives of compounds with phenol, aliphatic carboxylic acid, and aliphatic alcohol groups were stable in aqueous-phase analytical conditions. In chromatography, silyl derivatization decreased the polarity of polar compounds such as 4-hydroxybutyric acid (GHB), and enhanced chromatographic behavior in the reverse-phase C18 column. In addition, the silylation of aliphatic alcohol in GHB and 9-fluorenol (9-FLU) gave rise to a dramatic enhancement in ionization efficiency. Such enhancement was significantly observed in the mobile- phase including ammonium formate. The ionization efficiency of GHB and 9-FLU were increased by approximately 44 and 71 fold compared with non-derivatives, respectively. Their limit of detections (LODs) was lowered by 20 and 50 fold. The ionization efficiency enhancement was presumed to result from the increased gas-phase proton affinity (PA) originating from the electron-donating effect. In conclusion, the proposed silyl derivatization has great application potential in various research fields related to the analysis of small molecules.

This study was supported by an intramural grant from Korea Institute of Science and Technology