Pyragrel;
LC-MS/MS;
Human plasma;
Pharmacokinetics;
THROMBOXANE;
AGGREGATION;
ISCHEMIA;
OZAGREL;
D O I:
10.1016/j.jpba.2018.04.010
中图分类号:
O65 [分析化学];
学科分类号:
070302 ;
081704 ;
摘要:
Pyragrel is a novel thromboxane A2-synthetase inhibitor for the treatment of cerebral infarction, and it is currently being investigated in phase I clinical trials. This paper reports the first reliable LC-MS/MS method for the simultaneous determination of Pyragrel and its two main metabolites, M1 and M2, in human plasma. All analytes were extracted from human serum using liquid-phase extraction and separated on a Zorbax EcLipse XDB C18 column using isocratic elution with a mobile phase composed of methanol, water and formic acid (65:35:0.1, v/v/v). Determination of the analytes was achieved by tandem-mass spectrometry with positive electrospray ionization. The multiple reaction monitoring transitions under positive electrospray ionization were performed at m/z 329.0 -> m/z 135.9 for Pyragrel, m/z 303.1 -> m/z 135.0 for Ml, m/z 331.2 -> m/z 135.0 for M2, and 482.2 -> m/z 258.0 for IS, respectively. The following parameters were validated: specificity, recovery, matrix effects, carry-over, linearity, sample stability under a variety of storage and handling conditions, and stock solution stability. The validated method has been successfully applied to an initial pharmacokinetic study in healthy volunteers following intravenous administrations of 60 mg of Pyragrel, and this method will facilitate further studies involving more comprehensive identification of the metabolic profile of Pyragrel and the appropriate dosage regimen. (C) 2018 Elsevier B.V. All rights reserved.
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Fang, Weirong
;
Wei, Jie
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Wei, Jie
;
Han, Dan
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Han, Dan
;
Chen, Xi
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Chen, Xi
;
He, Guangwei
论文数: 0引用数: 0
h-index: 0
机构:
Hefei Yigong Med Co Ltd, Hefei 230088, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
He, Guangwei
;
Wu, Qiang
论文数: 0引用数: 0
h-index: 0
机构:
Hefei Yigong Med Co Ltd, Hefei 230088, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Wu, Qiang
;
Chu, Shaoxing
论文数: 0引用数: 0
h-index: 0
机构:
Hefei Yigong Med Co Ltd, Hefei 230088, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Chu, Shaoxing
;
Li, Yunman
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Sathler, Plino Cunha
;
Santana, Marcos
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Fluminense, Dept Mol & Cell Biol, BR-24210130 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Santana, Marcos
;
Lourenco, Andre Luiz
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Fluminense, Dept Mol & Cell Biol, BR-24210130 Rio De Janeiro, Brazil
Univ Fed Fluminense, Antonio Pedro Univ Hosp, Dept Pathol, BR-24210130 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Lourenco, Andre Luiz
;
Rodrigues, Carlos Rangel
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Rodrigues, Carlos Rangel
;
Abreu, Paula
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Abreu, Paula
;
Cabral, Lucio Mendes
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Cabral, Lucio Mendes
;
Castro, Helena Carla
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Univ Fed Fluminense, Dept Mol & Cell Biol, BR-24210130 Rio De Janeiro, Brazil
Univ Fed Fluminense, Antonio Pedro Univ Hosp, Dept Pathol, BR-24210130 Rio De Janeiro, Brazil
Univ Fed Fluminense, Dept Biotechnol, BR-24210130 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Fang, Weirong
;
Wei, Jie
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Wei, Jie
;
Han, Dan
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Han, Dan
;
Chen, Xi
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Chen, Xi
;
He, Guangwei
论文数: 0引用数: 0
h-index: 0
机构:
Hefei Yigong Med Co Ltd, Hefei 230088, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
He, Guangwei
;
Wu, Qiang
论文数: 0引用数: 0
h-index: 0
机构:
Hefei Yigong Med Co Ltd, Hefei 230088, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Wu, Qiang
;
Chu, Shaoxing
论文数: 0引用数: 0
h-index: 0
机构:
Hefei Yigong Med Co Ltd, Hefei 230088, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
Chu, Shaoxing
;
Li, Yunman
论文数: 0引用数: 0
h-index: 0
机构:
China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R ChinaChina Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Sathler, Plino Cunha
;
Santana, Marcos
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Fluminense, Dept Mol & Cell Biol, BR-24210130 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Santana, Marcos
;
Lourenco, Andre Luiz
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Fluminense, Dept Mol & Cell Biol, BR-24210130 Rio De Janeiro, Brazil
Univ Fed Fluminense, Antonio Pedro Univ Hosp, Dept Pathol, BR-24210130 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Lourenco, Andre Luiz
;
Rodrigues, Carlos Rangel
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Rodrigues, Carlos Rangel
;
Abreu, Paula
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Abreu, Paula
;
Cabral, Lucio Mendes
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Cabral, Lucio Mendes
;
Castro, Helena Carla
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil
Univ Fed Fluminense, Dept Mol & Cell Biol, BR-24210130 Rio De Janeiro, Brazil
Univ Fed Fluminense, Antonio Pedro Univ Hosp, Dept Pathol, BR-24210130 Rio De Janeiro, Brazil
Univ Fed Fluminense, Dept Biotechnol, BR-24210130 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Sch Pharm, Rio De Janeiro, Brazil