title: 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.
abstract: 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.
authors.affiliation: Indiana University Medical Center, Department of Pathology and Laboratory Medicine, Indianapolis 46202-5120.
authors.forename: D A
authors.initials: DA
authors.lastname: Whitman
authors.forename: V
authors.initials: V
authors.lastname: Abbott
authors.forename: K
authors.initials: K
authors.lastname: Fregien
authors.forename: L D
authors.initials: LD
authors.lastname: Bowers
mesh_terms: D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000032:analysis* / Q000493:pharmacokinetics; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000378:metabolism; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D013058:Mass Spectrometry
chemical_list: D016572:Cyclosporine