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.

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.