title: Determination of IMM-H004, a novel neuroprotective agent, in rat plasma and brain tissue by liquid chromatography-tandem mass spectrometry.
abstract: A rapid and sensitive liquid chromatography-tandem mass spectrometry method for determination of IMM-H004, a novel neuroprotective agent, in rat plasma and brain was developed. Plasma and brain tissue homogenate samples containing IMM-H004 and propranolol (internal standard, IS) were prepared by using a direct protein precipitation of acetonitrile. Separation was carried out in Zorbax SB-C18 column at a flow rate of 0.3mL/min utilizing acetonitrile/water as mobile phases which contain 0.5% formic acid (v/v). Triple quadrupole mass spectrometer was used for detection with selective reaction monitoring. The mass transition ion-pairs were 305→248 for IMM-H004 and 260→183 for IS in positive ion mode. The linear ranges of IMM-H004 were 5-1000ng/mL in plasma and 1-200ng/mL in brain tissue homogenate. The intra- and inter-day precisions were within ±14.9% for analyte in both matrices (±17.0% at the lowest limit of quantification level), while the deviation of assay accuracy was within ±12.9%. No obvious matrix effect was observed. The recovery of the analyte was higher than 85.3%. IMM-H004 was stable during the whole analytic process. The method was applied successfully to the plasma and brain pharmacokinetic study of IMM-H004 in rats after a single intravenous administration.
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: zhangziqian@imm.ac.cn.
authors.forename: Ziqian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Xiangmeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Manman
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, 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 Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Baolian
authors.initials: B
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: shengli@imm.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, 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: D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003374:Coumarins / Q000097:blood / Q000493:pharmacokinetics*; D057230:Limit of Detection; D008297:Male; D018696:Neuroprotective Agents / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003374:Coumarins; C588372:IMM-H004; D018696:Neuroprotective Agents
keywords: Brain; IMM-H004; LC–MS/MS; Pharmacokinetic; Plasma