title: Determination of a deuterohemin-peptide conjugate in rat plasma by liquid chromatography-tandem mass spectrometry and application to a preclinical pharmacokinetic study.
abstract: The deuterohemin-peptide conjugate (DhHP-6) is a microperoxidase mimetic, which has demonstrated substantial benefits in vivo as a scavenger of reactive oxygen species. This paper reports the development of a sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of DhHP-6 in rat plasma using triptorelin as an internal standard (IS). 50μL plasma was used in sample preparation, and a simple protein precipitation procedure with acetonitrile was involved. Satisfactory peak shapes of analyte and IS were obtained on an Agilent HC-C18 column by using a gradient elution with 10mM ammonium acetate-0.5% formic acid (v:v) and acetonitrile, there was no significant interference impacting the determination. A calibration curve obtained from this method was linear within the concentration range 10-3000ng/mL with intra- and inter-day precisions of 4.2-6.8% and 3.2-8.9%, respectively and accuracy of -1.3% to 2.1%. The recovery was above 80% with low matrix effects. The method was successfully applied to support a preclinical pharmacokinetic study in rat.
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Jilin University, Changchun 130021, PR China.
authors.forename: Yantong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Chemistry, Jilin University, Changchun 130021, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, PR China.
authors.forename: Chunxue
authors.initials: C
authors.lastname: Fang
authors.affiliation: School of Pharmacy, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Fawcett
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Rheumatology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Yin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, PR China. Electronic address: yyan@jlu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Research Center for Drug Metabolism, Jilin University, Changchun 130012, PR China; Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, PR China. Electronic address: gujk@mail.jlu.edu.cn.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D006427:Hemin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D010949:Plasma / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods; D017329:Triptorelin Pamoate / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D009842:Oligopeptides; C552681:deuterohemin-alanyl-histidyl-threonyl-valyl-glutamyl-lysine; D017329:Triptorelin Pamoate; D006427:Hemin
keywords: Deuterohemin–peptide conjugate; DhHP-6; LC–MS/MS; Pharmacokinetics