LC-MS/MS Analysis and Pharmacokinetics of Sodium (±)-5-Bromo-2-(α-hydroxypentyl) Benzoate (BZP), an Innovative Potent Anti-Ischemic Stroke Agent in Rats.
A rapid, sensitive and selective liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of sodium (±)-5-Bromo-2-(α-hydroxypentyl) benzoate (BZP) and its active metabolite 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in rat plasma using potassium 2-(1-hydroxypentyl)-benzoate (PHPB) and l-3-n-butylphthalide (NBP) as internal standards (IS). Chromatographic separation was achieved on a Hypersil GOLD C18 column using a gradient elution of ammonium acetate and methanol at a flow rate of 0.2 mL/min. Good linearity was achieved within the wide concentration range of 5-10,000 ng/mL. The intra-day and inter-day precision was less than 8.71% and the accuracy was within -8.53% and 6.38% in quality control and the lower limit of quantitation samples. BZP and Br-NBP were stable during the analysis and the storage period. The method was successfully applied to pharmacokinetic studies of BZP in Sprague-Dawley rats for the first time. After a single intravenous administration of BZP at the dose of 0.75 mg/kg, the plasma concentration of BZP and Br-NBP declined rapidly and the AUC0-t of BZP was significantly greater in female rats compared to male rats (p < 0.05). The data presented in this study serve as a firm basis for further investigation of BZP in both preclinical and clinical phases.
Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou 450052, Henan, China. tianx@zzu.edu.cn.|Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. tianx@zzu.edu.cn.
Xin
X
Tian
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, Henan, China. bingjiewait@163.com.
Bingjie
B
Liu
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, Henan, China. zhangyh228@163.com.
Yuhai
Y
Zhang
Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou 450052, Henan, China. jimlee_2007@126.com.
Hongmeng
H
Li
Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou 450052, Henan, China. 15981980136@163.com.
Jingyao
J
Wei
Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou 450052, Henan, China. wanggaoju@gs.zzu.edu.cn.
Gaoju
G
Wang
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, Henan, China. changjunbiao@zzu.edu.cn.
Junbiao
J
Chang
Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou 450052, Henan, China. qiaohl@zzu.edu.cn.
Hailing
H
Qiao
D000818:Animals; D001970:Bromobenzoates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D004195:Disease Models, Animal; D004355:Drug Stability; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy; D053719:Tandem Mass Spectrometry / Q000379:methods*
D001970:Bromobenzoates
BZP; Br-NBP; LC-MS/MS; metabolite; pharmacokinetics; rat plasma