Quantitative Determination of Synthesized Genotoxic Impurities in Nifuroxazide Capsules by Validated Chromatographic Methods

Abstract

Two accurate, selective, and precise chromatographic methods, namely TLC-densitometric and reversed-phase (RP)-HPLC, were developed and validated for the simultaneous determination of nifuroxazide (NIF) and its four synthesized impurities, which are also reported to be its related substances in the range of 10-100 μg/band and 10-100 μg/mL for NIF in the TLC and RP-HPLC methods, respectively. The developed TLC-densitometric method depended on the separation and quantitation of the studied components on silica gel 60 F254 TLC plates. Ethyl acetate-acetone-methanol-ammonia (85 + 25 + 5 + 0.5, v/v/v/v) was used as the developing system, and the separated bands were UV-scanned at 230 nm. On the other hand, the developed RP-HPLC method depended on chromatographic separation using a C8 column at 25°C and an aqueous solution of 0.1% sodium lauryl sulfate-acetonitrile as the mobile phase delivered according to the gradient elution program. Factors affecting the developed methods were studied and optimized. Also, method validation was carried out according to International Conference on Harmonization guidelines. The proposed methods were successfully applied for the determination of the studied drug in its bulk powder and in its pharmaceutical formulation. The developed methods showed no significant difference when compared with the reported RP-HPLC one. Their advantage is being the first stability-indicating methods for NIF and its genotoxic impurities.

Comparison of two augmented classical least squares algorithms and PLS for determining nifuroxazide and its genotoxic impurities using UV spectroscopy

“…It was prepared by 2 hours refluxing of (3.08 g, 20 mmol) of methyl 4‐hydroxybenzoate and (2.6 g, 50 mmol) of hydrazine hydrate in 100‐mL absolute ethanol. The white precipitate formed was filtered, washed, and dried …”

“…The physical and spectral data for all the prepared compounds were tested and elucidated by IR (KBr), 1 H‐NMR, and 13 C NMR …”

“…These methods include spectrophotometry, high‐performance liquid chromatography (HPLC), voltammetry, and differential pulse polarography . In our previous published work, NIF was determined by thin‐layer chromatography (TLC) and HPLC methods in the presence of its genotoxic impurities …”

Electrochemical stripping voltammetrical sensor based on polypyrrole exfoliated polyetheramine–montmorillonite nanocomposite for nanomolar detection of nifuroxazide

“…Due to the therapeutic significance of the NF, various analytical systems have been applied to evaluate its validity in commercial and biological fluids. 2–25 It is noteworthy that the two spectrofluorimetric methods 3,4 allow NF to be detected in either a single form or in a binary mixture with drotaverine. However, the drawback of the former 3 is that the method can not be applied for the determination of NF in presence of drotaverine, since the alkaline conditions required would lead to degradation of drotaverine 4 and thus the method requires intensive sample pretreatment.…”