Taguchi Approach for Optimization of a Green Quantitative 1H-NMR Practice for Characterization of Levetiracetam and Brivaracetam in Pharmaceuticals

Abstract

Background Recently, quantitative nuclear magnetic resonance (qNMR) competes with separation techniques like HPLC and capillary electrophoresis for quantification purposes when dealing with molecules that lack a chromophore. Objective The advantages of the proton nuclear magnetic resonance spectroscopy as a revolutionary quantitative analysis method were exploited aimed at simple and green assessment of two racetams namely, levetiracetam (LEV) and brivaracetam (BRV) as a new family of antiepileptic medications with unique mechanism of action. The developed technique was effectively utilized to determine LEV in Keppra tablets and BRV in laboratory prepared tablets without interfering with the ordinarily suspected excipients. Method Taguchi approach was applied as a powerful and user-friendly statistical technique for optimization of the qH1NMR experimental design for both drugs. The optimum acquisition conditions were number of scans 32, pulse angel 20° and relaxation delay of 40 sec for LEV and number of scans 128, pulse angle 90° and relaxation delay 1 sec for BRV. NMR Spectra were obtained by means of phloroglucinol as an internal standard and dimethyl sulfoxide-d6 as a solvent. Results The diagnostic doublet of doublet quantitative signals at 4.3 and at 4.2 ppm were chosen to estimate LEV and BRV respectively. The recovery of both drugs was quantified through the range of 0.1–12 mg/mL. The limits of detection were 0.013, 0.0013 and the limits of quantitation were 0.04, 0.0039 mg/mL for LEV and BRV correspondingly. Conclusions The suggested technique was fully validated according to ICH guidelines and proved to be an eco-friendly practice by means of three different assessment tools including; green analytical procedures index, national environmental methods index and analytical eco-scale. qH1NMR should be considered as a green alternative for quantification and quality control assessment of pharmaceuticals Highlights This research represents first simple, quick, and green alternative method for determination of both racetams in their pharmaceuticals.

Review on bioanalytical and analytical method development of Antiepileptic racetams

“…Proton nuclear magnetic resonance spectroscopy practice ( 1 H NMR) was applied to quantify LEV in either pure or pharmaceutically available tablets by scanning different experimental settings applying DOE as a statistical methodology (N. M. Mansour, D. T. El-Sherbiny, F. A. Ibrahim, & H. I. El-Subbagh, 2022b).…”