Recent Advances in High-Performance Liquid Chromatography/Mass Spectrometry and High-Performance Liquid Chromatography/Tandem Mass Spectrometry: Detection of Cyclosporine and Metabolites in Kidney and Liver Tissue

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Recent advances in both ionization methods and mass spectrometers have resulted in powerful new techniques for the study of drug metabolism and disposition. The interest in high-performance liquid chromatography/mass spectrometry (HPLC/MS) is the result of the lack of a sensitive universal detector for HPLC. Although it is not the ideal detector, HPLC/MS has become a reliable technique for xenobiotic analysis. The application of HPLC/MS to studies of the pharmacology and toxicology of molecules of mass <1,500 daltons is most advantageous in three areas: development of specific methods for trace analysis, detection and characterization of metabolites, and studies of interactions between drug molecules and peptides/proteins. We have used HPLC/MS to study the deposition of cyclosporine and its metabolites in needle biopsy samples from kidney and liver in which sample size is severely limited. The limit of detection in the single-ion monitoring mode was 500 fg (450 amol), which is about a thousandfold lower than UV limits of detection.

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