STUDIES ON DRUG-METABOLISM USING LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY - COMPARISON OF 3 LIQUID-CHROMATOGRAPHIC MASS-SPECTROMETRIC INTERFACES

Three ionization methods of liquid chromatography/mass spectrometry (L C/MS) \ atmospheric pressure chemical ionization (APCI), thermospray ( TSP) and electrospray ionization (ESI)\, were characterized by investi gating the relationships between sensitivities and polarities of compo unds. Log P values and mass spectrometry of three hydroxymethylglutary l-Coenzyme A (HMG-CoA) reductase inhibitors-pravastatin sodium (includ ing 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 io ns and sensitivities. The APCI method showed a high sensitivity of sev eral nanograms for hydrophobic compounds (log P > 2), but was not effe ctive for hydrophilic compounds, such as glutathione conjugate. The TS P method was found to be applicable to all compounds used in this stud y, and was more sensitive for hydrophobic compounds. The ESI method wa s 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 comp ounds. These results suggest that hydrophobicity of compounds related to efficiency of LC/MS ionization.