Titrimetric and spectrophotometric assay of oxcarbazepine in pharmaceuticals using N-bromosuccinimide and bromopyrogallol red

Abstract

Titrimetric and spectrophotometric methods are described for the determination of oxcarbazepine (OXC) in bulk drug and in tablets. The methods use N-bromosuccinimide (NBS) and bromopyrogallol red (BPR) as reagents. In titrimetry (method A), an acidified solution of OXC is titrated directly with NBS using methyl orange as indicator. Spectrophotometry (method B) involves the addition of known excess of NBS to an acidified solution of OXC followed by the determination of the unreacted NBS by reacting with BPR and measuring the absorbance of the unreacted dye at 460 nm. Titrimetry allows the determination of 6-18 mg of OXC and follows a reaction stoichiometry of 1 : 1 (OXC : NBS), whereas spectrophotometry is applicable over the concentration range of 0.8-8.0 μg mL(-1). Method B with a calculated molar absorptivity of 2.52 × 10(4) L mol(-1) cm(-1) is the most sensitive spectrophotometric method ever developed for OXC. The optical characteristics such as limits of detection (LOD), quantification (LOQ), and Sandell's sensitivity values are also reported for the spectrophotometric method. The accuracy and precision of the methods were studied on intraday and interday basis. The methods described could usefully be applied to routine quality control of tablets containing OXC. No interference was observed from common pharmaceutical adjuvants. Statistical comparison of the results with a reference method shows an excellent agreement and indicates no significant difference in accuracy and precision. The reliability of the methods was further ascertained by recovery studies in standard addition procedure.

Scheme 1

Hydrolysis of NBS to produce hypobromous acid/monovalent bromine.

Scheme 2

Suggested reaction pathway for the bromination of OXC.

Figure 1

Absorption spectra of BPR in sulphuric acid medium and the reagent blank (bromoderivative of the dye, BPR).

Figure 2

Study of reaction time between NBS and OXC in sulphuric acid medium and stability of the coloured species by measuring the absorbance of the unreacted BPR after reacting with NBS.

Scheme 3

Tentative reaction pathway for the formation of yellow coloured bromo-derivative of BPR (method B).