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Molecules 2016, 21(4), 501; doi:10.3390/molecules21040501

LC-MS/MS Analysis and Pharmacokinetics of Sodium (±)-5-Bromo-2-(α-hydroxypentyl) Benzoate (BZP), an Innovative Potent Anti-Ischemic Stroke Agent in Rats

1
Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou 450052, Henan, China
2
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
3
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, Henan, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 19 February 2016 / Revised: 30 March 2016 / Accepted: 7 April 2016 / Published: 16 April 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [1234 KB, uploaded 21 April 2016]   |  

Abstract

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. View Full-Text
Keywords: BZP; metabolite; Br-NBP; LC-MS/MS; pharmacokinetics; rat plasma BZP; metabolite; Br-NBP; LC-MS/MS; pharmacokinetics; rat plasma
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MDPI and ACS Style

Tian, X.; Liu, B.; Zhang, Y.; Li, H.; Wei, J.; Wang, G.; Chang, J.; Qiao, H. LC-MS/MS Analysis and Pharmacokinetics of Sodium (±)-5-Bromo-2-(α-hydroxypentyl) Benzoate (BZP), an Innovative Potent Anti-Ischemic Stroke Agent in Rats. Molecules 2016, 21, 501.

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