title: Quantitative determination of sirolimus in dog blood using liquid chromatography-tandem mass spectrometry, and its applications to pharmacokinetic studies.
abstract: A rapid, sensitive method of detecting sirolimus in blood was developed and applied in pharmacokinetic studies employing deionized water for hemolysis and a weakly basic mobile phase to enhance chromatographic peak intensity. Dog blood samples were processed via liquid-liquid extraction and the amounts of sirolimus and tacrolimus, an internal standard, were quantified by LC-MS/MS. Specificity, the lower limit of quantification, linearity, accuracy, precision, dilution, recovery, matrix effects, robustness and stability were within the acceptable range for assay validation. The concentration of sirolimus was quantifiable in blood samples for up to 36 h after the dog had received a 3 mg/kg dose of sirolimus. These observations suggest that sirolimus can be detected at low levels in dog blood using a basic mobile phase and metal-free hemolysis. This method is therefore applicable to pharmacokinetic studies in dogs.
authors.affiliation: Research and Development Division, Korea Institute of Toxicology, Daejeon, Republic of Korea.
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Cha
authors.forename: Wonkyung
authors.initials: W
authors.lastname: Cho
authors.forename: Junsung
authors.initials: J
authors.lastname: Park
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: Youngseok
authors.initials: Y
authors.lastname: Cho
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D004355:Drug Stability; D007166:Immunosuppressive Agents / Q000097:blood*; D057230:Limit of Detection; D020123:Sirolimus / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus