Studies on drug metabolism using liquid chromatography/mass spectrometry: Comparison of three liquid chromatographic/mass spectrometric interfaces

Three ionization methods of liquid chromatography/mass spectrometry (LC/MS) [atmospheric pressure chemical ionization (APCI), thermospray (TSP) and electrospray ionization (ESI)], were characterized by investigating the relationships between sensitivities and polarities of compounds. Log P values and mass spectrometry of three hydroxymethylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors—pravastatin sodium (including its metabolites and related compounds), lovastatin and simvastatin—were measured. Their log P values ranged from −2.49 to 4.40, and in LC/MS each of the ionization methods gave different quasi-molecular ions and sensitivities. The APCI method showed a high sensitivity of several nanograms for hydrophobic compounds (log P > 2), but was not effective for hydrophilic compounds, such as glutathione conjugate. The TSP method was found to be applicable to all compounds used in this study, and was more sensitive for hydrophobic compounds. The ESI method was also applicable to all compounds (up to 20 ng), and was 10–100 times more sensitive than the other methods in the case of hydrophilic compounds. These results suggest that hydrophobicity of compounds related to efficiency of LC/MS ionization.