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Molecules 2016, 21(4), 501;

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

Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou 450052, Henan, China
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
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)
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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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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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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