Abstract
Objective: A liquid chromatography-tandem mass spectrophotometric (LC–MS/MS) method was developed for quantification of brivaracetam in rabit plasma employing liquid-liquid extraction with ethyl acetate.Methods: Developed method was validated for specificity, precision, accuracy, recovery, and stability characteristics. Chromatographic separation was achieved on Chromolith C18column (100 mmx4.6 mmx5 µm) with 0.1% formic acid, adjusted to pH 3.2 as an isocratic mobile phase with a flow rate of 1.0 ml/min. the developed method was applied to assess pharmacokinetics parameters like Cmax, Tmax, t1/2 and AUC of brivaracetam in healthy rabbits.Results: The developed method was linear over the range of 0.16 to 8µg/ml. The regression equation for the analysis was Y=0.0053x+0.0018 with coefficient of correction (r2) = 0.998. The % mean recovery for brivaracetam was found to be between 95.7% to 106.5%. The mean intraday and inter-day precision of the method was found to be 0.77 to 3.72% for quality control standards. Brivaracetam showed Tmax of 1.025±0.061 and mean Cmax, AUC0®t andAUC0®a for Test formulation is 92.7±4.4, 496.21±26.4 and 504.20±30.68 respectively.Conclusion: A highly specific, rugged and rapid method with sufficiently low LLOQ was developed for analysis of routine samples of a single dose or multiple dose pharmacokinetic studies with any marketing formulation of brivaracetam.
Highlights
Acute seizures are a common occurrence in the intensive care unit (ICU), either as a primary reason for admission or as a neurologic complication of a severe metabolic disorder or critical illness state
The established LLOQ is sufficiently low to conduct a pharmacokinetic study with any marketing formulation of brivaracetam in human volunteers
Brivaracetam showed to maximum plasma concentration (Tmax) of 1.025±0.061 and mean Cmax, AUC0→t and AUC0→α for Test formulation is 92.7±4.4, 496.21±26.4 and 504.20±30.68 respectively the results were presented in table 5, table 6 and fig. 6
Summary
Acute seizures are a common occurrence in the intensive care unit (ICU), either as a primary reason for admission or as a neurologic complication of a severe metabolic disorder or critical illness state. Rapid identification of acute seizures must be followed by immediate treatment with a fast-acting antiepileptic drug (AED). This is essential to reduce potential sequelae, ischemic and excitotoxic neuronal cell loss, which begins within minutes of continuous seizure activity [1]. Fast-acting benzodiazepines are the preferred first-line treatment of acute seizures and SE [2]. Literature survey pharmacokinetics and metabolism of 14C-brivaracetam, metabolism studies of brivaracetam and gemfibrozil, clinical trials of adjunctive brivaracetam for refractory partial-onset seizures, identification of drug metabolites in human plasma or serum integrating metabolite prediction, by LC– HRMS methods are reported for the drug [9,10,11,12,13]. The established LLOQ is sufficiently low to conduct a pharmacokinetic study with any marketing formulation of brivaracetam in human volunteers
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