title: Quantification of OSU-2S, a novel derivative of FTY720, in mouse plasma by liquid chromatography-tandem mass spectrometry.
abstract: OSU-2S is a novel anti-cancer and immune modulatory agent designed specifically to avert the immunosuppressive effects and related toxicities observed in clinical studies with its predecessor analog, FTY720. To characterize its preclinical pharmacokinetics, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of OSU-2S in mouse plasma. Ethyl acetate extraction of samples containing OSU-2S and the internal standard, Sph-17, was followed by separation with a 6min gradient (water/0.1% formic acid and methanol/0.1% formic acid) on a reverse-phase C18 column at room temperature. Selected reaction monitoring was used for detection on a triple quadrupole mass spectrometer with positive ionization. The assay was linear over the concentration range 3-3000ng/mL with accuracy ranging from 103 to 111%, and both within- and between-run precision (CV%) ≤11%. All stability samples were within ±15% of nominal values, and replicates were within 15% CV. The assay was successfully applied to a mouse pharmacokinetic study of OSU-2S with intravenous and intraperitoneal administration. OSU-2S non-compartmental pharmacokinetic parameters, area under the concentration-time curve, clearance, and elimination half-life were estimated at 1522hμg/L, 3.06L/h/kg and 15.6h, respectively, for intravenous injection. Systemic availability after intraperitoneal injection was approximately 46%. These data demonstrate the OSU-2S compound displays acceptable pharmacokinetic properties for further in vivo pharmacologic evaluation, which can be facilitated by the validated LC-MS/MS assay.
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA; Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Mao
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ribai
authors.initials: R
authors.lastname: Yan
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA; Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH 43210, USA; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address: raj.muthusamy@osumc.edu.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Muthusamy
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. Electronic address: mitch.phelps@osumc.edu.
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Phelps
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D000068876:Fingolimod Hydrochloride; D006207:Half-Life; D051379:Mice; D008813:Mice, Inbred ICR; D010949:Plasma / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: C560545:OSU-2S; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: FTY720; Liquid chromatography–tandem mass spectrometry; Mouse; OSU-2S; Pharmacokinetics