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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(3 H )-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  AUC  0-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.

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