A Validated Lc-MS/MS Method for Pharmacokinetic Study of Brivaracetam in Healthy Rabbits

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 (r 2 ) = 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 and AUC0→α 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.

Simple and efficient method for the quantification of antiepileptic drugs in human plasma by using magnetic graphene oxide-β-cyclodextrin composite as a sorbent

“…Therefore, the solid-phase extraction method is considered as an alternative method for the analysis of drugs in the plasma due to its good extraction ability, convenient operation, and consumption of a low amount of organic solvents and it needs a low amount of adsorbent. Compared with earlier reported methods by using different equipments, our method showed high precision, wider linear range, and comparable detection limit (see Table 4) [16,[37][38][39][40][41][42][43][44]. These results demonstrate the advantages of the current method over the available methods, and in addition to this, there were no studies that reported on the simultaneous extraction of these three antiepileptic drugs using the solid-phase extraction method.…”

Identification, isolation, structural characterisation, synthesis and in silico toxicity prediction of the alkaline hydrolytic degradation product of brivaracetam by using LC-PDA, preparative HPLC, LC/HESI/LTQ, FTIR, and 1H NMR

“…3 A literature survey reveals that very few analytical methods are available for brivaracetam. [4][5][6][7][8]20 Brivaracetam is primarily metabolized by the hydrolysis of the acetamide moiety to form a carboxylic acid metabolite. 9 Brivaracetam binds SV2A with high affinity.…”

A Brief Review of Analytical Methods for the Estimation of Brivaracetam in Pharmaceutical Formulation and Biological Matrices

“…Hyphenated Techniques: LC-MS/MS LC-MS/MS has been developed by D Atul Vasanth et al, (24) for assessing the pharmacokinetics of BRV in healthy rabbits. In this study, the authors used the Chromolith C18column (100 x4.6 mm 5 μm) containing 0.1% formic acid, adjusted to pH 3.2 with a flow rate of 1.0 ml/min as an isocratic mobile phase.…”