title: Simultaneous determination of SYL-1119 and SYL-1119-P in rat plasma using HPLC coupled with tandem mass spectrometry.
abstract: SYL-1119 is a sphingosine-1-phosphate receptor 1 modulator for the treatment of autoimmune disease with better selectivity, while SYL-1119-P is its active phosphate. A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of SYL-1119 and SYL-1119-P in rat plasma. SYL-1110, an analogue of SYL-1119, was used as the internal standard. Plasma samples were prepared by protein precipitation using acetonitrile. The analytes and internal standard were separated on a Zorbax SB-C18 column (3.5μm, 100mm×2.1mm) with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2ml/min with an operating temperature of 20°C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode of the transitions at m/z 364→259 for SYL-1119, m/z 444→259 for SYL-1119-P, and m/z 378→273 for the IS. Calibration curves were linear in the range of 0.2-50ng/ml for SYL-1119 and 10-1000ng/ml for SYL-1119-P. The lower limit of quantification (LLOQ) was 0.2ng/ml for SYL-1119 and 10ng/ml for SYL-1119-P. The intra- and inter-day precisions were 5.4-12.8% for two analytes with accuracies within ±10%. The recoveries for two compounds were 91.3-104.5%. The analytes were proved to be stable during all sample storage, preparation, and analytic procedures. The method was successfully applied to the pharmacokinetic study of SYL-1119 and SYL-1119-P in rats after oral administration of SYL-1119.
authors.affiliation: Beijing City Key Laboratory of Active Substances Discovery and Drugability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism of Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Beijing City Key Laboratory of Active Substances Discovery and Drugability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism of Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.affiliation: Beijing City Key Laboratory of Active Substances Discovery and Drugability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism of Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: yanli@imm.ac.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D010710:Phosphates / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001713:Biphenyl Compounds; D010710:Phosphates; D049349:Receptors, Lysosphingolipid; C000591252:SYL-1119
keywords: LC–MS/MS; Pharmacokinetic; SYL-1119; SYL-1119-P