Development and Validation of Stability-Indicating HPLC Method for the Quantification of Levetiracetam in Bulk and Oral
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Pharmaceutical Chemistry Journal, Vol. 54, No. 8, November, 2020 (Russian Original Vol. 54, No. 8, August, 2020)
DEVELOPMENT AND VALIDATION OF STABILITY-INDICATING HPLC METHOD FOR THE QUANTIFICATION OF LEVETIRACETAM IN BULK AND ORAL SOLUTION: APPLICATION TO CHEMICAL KINETICS Sandeep S. Sonawane,1,* Santosh S. Chhajed,2 Dipika R. Jadhav,1 Nilima A. Thombre,3 and Sanjay J. Kshirsagar3 Original article submitted October 11, 2019. In the present study, a simple, accurate, precise and specific stability-indicating LC method was developed and validated for the quantification of levetiracetam (LEV) in bulk and oral solution. LEV and its degradation products were separated and resolved successfully on C18 column using a methanol:water (30:70 %, v/v) mixture in the isocratic mode at a flow rate of 1 mL/min. All eluents were detected at 205 nm. In forced degradation experiments, LEV was found to degrade significantly in acid, alkali, wet heat, peroxide mediated oxidation, and photolytic conditions, and found stable under dry heat conditions. Validation experiments showed acceptable accuracy, precision, and specificity of the developed method. Assay of the oral solution was in good agreement with the amount of LEV as per the label claim. The method was applied to investigate chemical kinetics under acid and alkali hydrolysis and the pH rate profile of LEV within a range of pH 2 – 12. Keywords: levetiracetam; HPLC; Briton – Robinson buffer; validation.
onset seizures [5]. Various theories have been proposed that LEV appears to act via binding to synaptic vesical protein 2A rather than binding to GABA or benzodiazepine receptors like other AEDs. This synaptic vesical protein is an integral membrane protein present on synaptic vesicles and some neuroendocrine cells. This inhibits the release of calcium from intraneuronal stores, opposing the activity of negative modulators of GABA and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, LEV inhibits N-type calcium channels [6, 7]. The literature survey revealed several analytical methods for the estimation of LEV in tablets [8, 9], stability-indicating methods for the estimation of LEV in tablets with its degradation products [10 – 14], and estimation of LEV in various biological fluids [15 – 17]. In the present work, a simple, accurate, precise and selective stability-indicating HPLC method was developed and validated for the quantitation of LEV in bulk and oral solution. The method was examined for its specificity and stability-indicating properties by resolving the drug from its forced degradation products. The developed method was applied to a detailed study of the chemical kinetics of LEV under acid and alkali hydrolysis conditions. The reaction rate constant (K) and half-life (t1/2), shelf-life (t90) were calculated in each case and the Arrhenius plot was obtained to estimate the energy of activation. In addition, the
1. INTRODUCTION The purpose of stability testing is to provide evidence on how the quality of a drug substan
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