title: Liquid chromatographic method for the determination of sirolimus in blood using electrochemical detection.
abstract: Therapeutic drug monitoring of sirolimus (rapamycin) is important for immunosuppressive therapy in solid organ transplantation. We have developed a simple and reliable method for determining blood concentrations of sirolimus using reversed-phase HPLC with electrochemical detection (ECD). The E(2) potential was set at +900 mV. The potential of guard cell was set at +950 mV and that of the E(1) cell at +400 mV. The method was linear for a concentration range of 1-50 ng/mL when 0.5 mL blood was used. The correlation coefficients of all standard curves were greater than or equal to 0.999. The limit of detection was 0.5 ng/mL. The inter-assay precision ranged from 3.22 to 7.48%, and the coefficient of variation (CV) for a quality control sample at 10 ng/mL was 7.48% with a bias of 8.4% from the target value. The intra-assay precision ranged from 0.72 to 3.71%, and the CV for a quality control sample at 10 ng/mL was 0.72% with a bias of 6.8% from the target value. In a solid organ transplant recipient, trough concentrations of sirolimus were well within the analytic range of the HPLC/ECD procedure. The method described here is suitable for management of sirolimus therapy in solid organ transplantation.
authors.affiliation: Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Etsuko
authors.initials: E
authors.lastname: Suka
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Akimoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohno
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishino
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D055664:Electrochemical Techniques / Q000379:methods*; D007166:Immunosuppressive Agents / Q000097:blood*; D016018:Least-Squares Analysis; D016014:Linear Models; D008956:Models, Chemical; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000097:blood*; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D007166:Immunosuppressive Agents; C058028:immunomycin; D020123:Sirolimus; D016559:Tacrolimus