Complexation of simvastatin (SV) with alpha, beta-cyclodextrins (CDs) was studied by means of UV spectrometry and ESI-mass spectrometry. The experimental results showed that stable 1:1 inclusion complexes between two CDs and SV were formed. In addition, the 1:2 complex between beta-CD and SV was observed. Semi-empirical PM3 calculations were performed to elucidate the different inclusion behaviors between SV and CDs. The calculation results indicated that the formations of some conventional hydrogen bonds and C-(HO)-O-... interactions (weak H bond) were the main factors for the non-covalent CD:SV complex formation and stabilization in gas phase. (c) 2005 Elsevier B.V. All rights reserved.