title: Quantitative determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'-biphenyl]-4-yl)ethyl)propane-1,3-diol and its active phosphorylated metabolite in rat blood by LC-MS/MS and application to PK/PD analysis.
abstract: A sensitive and specific LC-MS/MS method was developed and validated for simultaneous determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'-biphenyl]-4-yl)ethyl)propane-1,3-diol (SYL930) and its active phosphate metabolite (SYL930-P) in rat blood using SYL927, an analogue of SYL930 as the internal standard. Blood samples were prepared by a simple protein precipitation with acetonitrile. The chromatographic separation was performed on a ZorbaxSB-C18 column (3.5 μm, 2.1 × 100 mm) with a gradient mobile phase of methanol/water containing 0.1 % formic acid (v/v) at a flow rate of 0.2 mL/min. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) in multiple reactions monitoring mode (MRM). The monitored transitions were 381.2 → 364.2 for SYL930, 461.2 → 334.2 for SYL930-P, and 367.1 → 350.4 for the internal standard, respectively. Good linearity was obtained for the analytes over the range of 0.2-100 ng/mL for SYL930 and 0.5-100 ng/mL for SYL930-P. The lower limits of quantitation (LLOQs) for SYL930 and SYL930-P were 0.2 and 0.5 ng/mL, respectively. The intra-day and inter-day precisions (RSD, %) of analytes were within 9.87 %, and the accuracy (RE, %) ranged from -7.04 to 13.15 %. The mean recoveries for two compounds in rat blood were 87.9-109 %. The analytes were proved to be stable during all sample storage, preparation, and analytic procedures. The validated method was successfully applied to pharmacokinetic and PK/PD studies of SYL930 and SYL930-P in rats after oral administration of SYL930. Graphical Abstract Quantitative determination of SYL930 and its active phosphorylated metabolite in rat blood by LCMS/MS and application to PK/PD analysis.
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Manman
authors: M
authors: Zhao
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Jiaqi
authors: J
authors: Mi
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Dan
authors: D
authors: Li
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Xin
authors: X
authors: Liu
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Shuang
authors: S
authors: Yang
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Baolian
authors: B
authors: Wang
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Li
authors: L
authors: Sheng
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Xiaojian
authors: X
authors: Wang
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China.
authors: Jing
authors: J
authors: Jin
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China. hujp@imm.ac.cn.
authors: Jinping
authors: J
authors: Hu
authors: Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing, 100050, China. yanli@imm.ac.cn.
authors: Yan
authors: Y
authors: Li
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D010080:Oxazoles / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics; D010766:Phosphorylation; D011407:Propane / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C000608455:2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-(1,1'-biphenyl)-4-yl)ethyl)propane-1,3-diol; D010080:Oxazoles; D011407:Propane
keywords: 2-Amino-2-(2-(4′-(2-propyloxazol-4-yl)-[1,1′-biphenyl]-4-yl)ethyl)propane-1,3-diol; LC–MS/MS; PK/PD; Pharmacokinetics; Phosphorylated metabolite