title: A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application.
abstract: BACKGROUND
  This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode.
  
  
  METHODS
  Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 µL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm×2.1 mm i.d., 2.6-µm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode.
  
  
  RESULTS
  The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R(2)>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance.
  
  
  CONCLUSIONS
  A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.
authors.affiliation: Clinical Trial Center, Clinical Research Institute, Samsung Medical Center, Korea.
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Korea. ; Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Korea.
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Clinical Trial Center, Clinical Research Institute, Samsung Medical Center, Korea.
authors.forename: EunGi
authors.initials: E
authors.lastname: Cho
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Korea.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Korea.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ko
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Korea. ; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
mesh_terms: D001774:Blood Chemical Analysis / Q000295:instrumentation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D011786:Quality Control; D012015:Reference Standards; D013386:Succinates / Q000097:blood* / Q000378:metabolism / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D013386:Succinates; C064294:sarpogrelate
keywords: Clinical study; Core-shell-type chromatography; Metabolite; Sarpogrelate; Simultaneous determination