title: Development of a fast LC-MS/MS assay for the determination of deferiprone in human plasma and application to pharmacokinetics.
abstract: A fast and accurate liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay was first developed and validated for the determination of deferiprone in human plasma. The analytes were extracted with acetonitrile from only 50 μL aliquots of human plasma to achieve the protein precipitation. After extraction, chromatographic separation of analytes in human plasma was performed using a Synergi Fusion-RP 80A column at 30 °C. The mobile phase consisted of methanol and 0.2% formic acid containing 0.2 mM EDTA (60:40, v/v). The flow rate of the mobile phase was 0.8 mL/min. The total run time for each sample analysis was 4 min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the precursor-to-parent ion transitions m/z 140.1 → 53.1 for deferiprone and m/z 143.1 → 98.1 for internal standard. A linear range was established from 0.1 to 20 µg/mL. The limit of detection was determined as 0.05 µg/mL. The validated method was estimated for linearity, recovery, stability, precision and accuracy. Intraday and interday precisions were 4.3-5.5 and 4.6-7.3%, respectively. The recovery of deferiprone was in the range of 80.1-86.8%. The method was successfully applied to a pharmacokinetic study of deferiprone in six thalassemia patients.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan.
authors.forename: Ta-Shu
authors.initials: TS
authors.lastname: Song
authors.forename: Yow-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.forename: Ching-Tien
authors.initials: CT
authors.lastname: Peng
authors.forename: Cheng-Hsiung
authors.initials: CH
authors.lastname: Liu
authors.forename: Tai-Lin
authors.initials: TL
authors.lastname: Chen
authors.forename: Mann-Jen
authors.initials: MJ
authors.lastname: Hour
mesh_terms: D000293:Adolescent; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D000077543:Deferiprone; D004355:Drug Stability; D005260:Female; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D010865:Pilot Projects; D011728:Pyridones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D011728:Pyridones; D000077543:Deferiprone