In the past few years, high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) has matured to a true alternative to antibody-based immunoassays in routine therapeutic drug monitoring. In transplantation medicine, mass spectrometry-based assessment of immunosuppressant drug levels is considered a gold standard diagnostic procedure. We describe a fast state-of-the-art routine online solid-phase extraction (SPE) HPLC-MS/MS analysis platform that allows monitoring of cyclosporine A, tacrolimus, sirolimus and everolimus from 50-microl aliquots of EDTA whole blood specimens within 3.4 min total analysis time. Sample purification is done by offline protein precipitation followed by two automated chromatographic separation steps. Mass spectrometry-based analyte quantification relies on selected reaction monitoring experiments. The assay underwent complete validation and performance evaluation studies and performs very well in several international proficiency testing schemes. In daily routine, it allows reporting of about 75 patient sample results per work shift with a typical total individual sample turnaround time of less than 3 h.

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Enzyme inhibiting activity X 0220 SAR, Species Specificity, and Cellular Activity of Cyclopentene Dicarboxylic Acid Amides as DHODH Inhibitors. -Among the new compounds, derivative (Id) shows an IC50 value of 7nM on human DHODH. -(LEBAN*, J.; KRALIK, M.; MIES, J.; GASSEN, M.; TENTSCHERT, K.; BAUMGARTNER, R.; Bioorg. Med. Chem. Lett. 15 (2005) 21, 4854-4857; 4SC AG, D-82152 Martinsried, Germany; Eng.) -K. Schneider 05-235