Coupling capillary electrophoresis-electrospray ionization mass spectrometry with sheathless interface for drug analysis

Abstract

Capillary electrophoresis-mass spectrometry （CE-MS） combines the advantages of capillary electrophoresis， such as the high separation efficiency and low sample consumption， and the high detection sensitivity of mass spectrometry and the ability for providing the structural information for structure elucidation of unknown components. However， the interface technology for coupling capillary electrophoresis and mass spectrometry is still not well resolved. In the present work， we explored the application of the sheathless CE-MS interface which was prepared by gold foil-wrapped CE separation column tip directly as a spray electrode for the analysis of five tyrosine kinase inhibitors， namely sunitinib， imatinib mesylate， gefitinib， dasatinib and erlotinib. This interface integrates separation and electrospray ionization in one capillary， which is easy to manufacture， low in cost， and can be produced in batches. We found that using the nonaqueous CE separation mode can not only achieve baseline separation of five tyrosine kinase inhibitors， but also obtain stable mass spectrometry signals. First， we investigated the effect of the electrolyte solution composition on the separation. The optimized background electrolyte composition was obtained： 2% （v/v） acetic acid and 5 mmol/L ammonium acetate in acetonitrile-methanol （80∶20， v/v）. Under optimized conditions， the five kinase inhibitors could be baseline separated， meantime， the sheathless interface could also maintain stable electrospray for a long time. The relative standard deviation （RSD） values of the intraday and interday repeatability of the analyte retention times were less than 0.5% and 0.8%， respectively， and the RSD value between interface batches is less than 2.6%. Compared with CE-MS with aqueous phase， the separation column efficiency of the five tyrosine kinase inhibitors under nonaqueous phase conditions is higher， the detection sensitivity is higher， and the absolute detection limit reaches amol level. In addition， we evaluated the sheathless interface with various organic acids， such as palaflin A， salvianolic acid C， and rosmarinic acid， as well as hydrophobic macrolide antibiotics， azithromycin， erythromycin， and sporin A， good separation effect and mass spectrometric detection results can be obtained.