title: Dried blood spot analysis of creatinine with LC-MS/MS in addition to immunosuppressants analysis.
abstract: In order to monitor creatinine levels or to adjust the dosage of renally excreted or nephrotoxic drugs, the analysis of creatinine in dried blood spots (DBS) could be a useful addition to DBS analysis. We developed a LC-MS/MS method for the analysis of creatinine in the same DBS extract that was used for the analysis of tacrolimus, sirolimus, everolimus, and cyclosporine A in transplant patients with the use of Whatman FTA DMPK-C cards. The method was validated using three different strategies: a seven-point calibration curve using the intercept of the calibration to correct for the natural presence of creatinine in reference samples, a one-point calibration curve at an extremely high concentration in order to diminish the contribution of the natural presence of creatinine, and the use of creatinine-[(2)H3] with an eight-point calibration curve. The validated range for creatinine was 120 to 480 μmol/L (seven-point calibration curve), 116 to 7000 μmol/L (1-point calibration curve), and 1.00 to 400.0 μmol/L for creatinine-[(2)H3] (eight-point calibration curve). The precision and accuracy results for all three validations showed a maximum CV of 14.0% and a maximum bias of -5.9%. Creatinine in DBS was found stable at ambient temperature and 32 °C for 1 week and at -20 °C for 29 weeks. Good correlations were observed between patient DBS samples and routine enzymatic plasma analysis and showed the capability of the DBS method to be used as an alternative for creatinine plasma measurement.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Laboratory for Clinical and Forensic Toxicology and Drugs Analysis, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands, r.koster@umcg.nl.
authors.forename: Remco A
authors.initials: RA
authors.lastname: Koster
authors.forename: Ben
authors.initials: B
authors.lastname: Greijdanus
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Touw
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D003404:Creatinine / Q000097:blood*; D006400:Hematocrit; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D057230:Limit of Detection; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine