Determination of IMM-H004 and its active glucuronide metabolite in rat plasma and Ringer's solution by ultra-performance liquid chromatography-tandem mass spectrometry.

Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
PMID: 29329091

Abstract

IMM-H004 is a novel neuroprotective agent and its glucuronide metabolite IMM-H004G has similar protective effects against cerebral ischemic injury in vivo and in vitro. A specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was established and validated for determination of IMM-H004 and IMM-H004G simultaneously in rat plasma and Ringer's solution. Plasma samples containing IMM-H004, IMM-H004G and internal standard propranolol were prepared by direct protein precipitation in a sample-to-solvent ratio of 1:2:6 (plasma: water: acetonitrile), whereas no protein precipitation was required for Ringer's solution samples. Separation was performed with a gradient mobile phase of methanol/water with 0.5% formic acid (v/v) on Eclipse Plus C18 column (2.1×50mm, 3.5μm) at a flow rate of 0.3mL/min. The detection was operated on a triple quadrupole mass spectrometer in positive ion multiple reaction monitoring (MRM) mode. The monitored transitions were 305.1→248.1 for IMM-H004, 481.3→305.1 for IMM-H004G and 260.1→183.1 for propranolol. The linear ranges of IMM-H004 and IMM-H004G were 5 to 3000ng/mL and 10 to 3000ng/mL for plasma method and 0.5 to 500ng/mL for Ringer's solution method. All the intra-day and inter-day precision and accuracy for the two analytes in rat plasma were below 7.5% and the intra-day precision and accuracy for analytes in Ringer's solution were within ±14.7%. There was no obvious matrix effect and the recoveries of the analytes were higher than 94.2%. IMM-H004 and IMM-H004G were stable during one analytic process. The established method was applied successfully to plasma pharmacokinetic and brain microdialysis studies of IMM-H004 and IMM-H004G in rats after a single intravenous administration of IMM-H004.

Authors

  • Jianwei Jiang
    Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; 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.
  • Ziqian Zhang
    Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; 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.
  • Xiaowen Zou
    Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; 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.
  • Rui Wang
    Department of Clinical Laboratory Medicine Center, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China.
  • Jie Bai
    Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; 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.
  • Shengyu Zhao
    Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; 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.
  • Xiaoqing Fan
    Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; 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.
  • Li Sheng
    Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; 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. Electronic address: shengli@imm.ac.cn.
  • Yan Li
    Interdisciplinary Research Center for Biology and Chemistry, Liaoning Normal University, Dalian, China.

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