title: A sensitive and practical LC-MS/MS method for the determination of mizoribine in human serum and its bioequivalence study on Chinese healthy volunteers.
abstract: A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of mizoribine in human serum using thiamphenicol as internal standard (IS). The serum samples of mizoribine were precipitated with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase of 0.1% ammonium acetate water solution-methanol (47:53, v/v). Mizoribine and IS were detected in the multiple reaction monitoring mode with precursor/product ion transitions of m/z 258.2/126.0 and 354.1/185.2, respectively. The calibration curves were linear over the range of 0.02-2 microg mL(-1) for mizoribine. The limit of quantification (LOQ) was 0.02 microg mL(-1) with acceptable precision and accuracy. The validated method was successfully applied for the evaluation of a bioequivalence study on Chinese healthy volunteers. The main pharmacokinetics parameters after oral administration of 100 mg mizoribine test or reference formulation were as follows: Cmax (1.00 +/- 0.21), (1.00 +/- 0.22) microg mL(-1); AUC(0-infinity) (6.72 +/- 1.39), (6.48 +/- 1.44) microg h mL(-1); t1/2 (2.77 +/- 0.26), (2.66 +/- 0.29) h; tmax (2.95 +/- 0.78), (2.84 +/- 0.50) h.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Zhao
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Yang
authors.forename: Xiang-hong
authors.initials: XH
authors.lastname: Li
authors.forename: Guo-guang
authors.initials: GG
authors.lastname: Mao
authors.forename: Xiao-quan
authors.initials: XQ
authors.lastname: Liu
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016001:Confidence Intervals; D004791:Enzyme Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D012263:Ribonucleosides / Q000097:blood* / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine