title: Simultaneous determination of sarpogrelate and its active metabolite in human plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.
abstract: We established a rapid and simple liquid chromatography with tandem mass spectrometry method for the simultaneous determination of sarpogrelate and its active metabolite, M-1, in human plasma. Sarpogrelate, M-1, and the internal standard, ketanserin, were extracted from a 50 μL aliquot of human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on a Shim-pack GIS ODS C18 column (100 × 3.0 mm; 3 μm) with an isocratic mobile phase consisting of 10 mM ammonium acetate and acetonitrile (70:30, v/v) at a flow rate of 0.6 mL/min; the total run time was <2.5 min. Mass spectrometric detection was conducted in selected reaction-monitoring mode with positive electrospray ionization at m/z 430.35 → 135.10 for sarpogrelate, m/z 330.30 → 58.10 for M-1, and m/z 395.70 → 188.85 for ketanserin. The linear ranges of concentration for sarpogrelate and M-1 were 1-1000 and 0.5-500 ng/mL, respectively. The coefficient of variation for the assay's precision was ≤9.95%, and the accuracy was 90.6-107%. All analytes were stable under various storage and handling conditions, and no relevant crosstalk and matrix effect was observed. This method was successfully applied to a pharmacokinetic study after oral administration of a 100 mg sarpogrelate tablet to healthy male Korean volunteers.
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, Republic of Korea.
authors.forename: Jung Bae
authors.initials: JB
authors.lastname: Park
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Bae
authors.forename: Euichaul
authors.initials: E
authors.lastname: Oh
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008297:Male; D012702:Serotonin Antagonists / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D013386:Succinates / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate
keywords: Active metabolites; human plasma; method validation; pharmacokinetics; sarpogrelate