Development and Application of a Validated Stability-Indicating High-Performance Liquid Chromatographic Method Using Photodiode Array Detection for Simultaneous Determination of Granisetron, Methylparaben, Propylparaben, Sodium Benzoate, and Their Main Degradation Products in Oral Pharmaceutical Preparations

Abstract

A simple, rapid, and sensitive RP-HPLC method using photodiode array detection was developed and validated for the simultaneous determination of granisetron hydrochloride, 1-methyl-1H-indazole-3-carboxylic acid (the main degradation product of granisetron), sodium benzoate, methylparaben, propylparaben, and 4-hydroxybenzoic acid (the main degradation product of parabens) in granisetron oral drops and solutions. The separation of the compounds was achieved within 8 min on a SymmetryShield RP18 column (100 x 4.6 mm id, 3.5 microm particle size) using the mobile phase acetonitrile--0.05 M KH2PO4 buffered to pH 3 using H3PO4 (3+7, v/v). The photodiode array detector was used to test the purity of the peaks, and the chromatograms were extracted at 240 nm. The method was validated, and validation acceptance criteria were met in all cases. The robust method was successfully applied to the determination of granisetron and preservatives, as well as their degradation products in different batches of granisetron oral drops and solutions. The method proved to be sensitive for determination down to 0.04% (w/w) of granisetron degradation product relative to granisetron and 0.03% (w/w) 4-hydroxybenzoic acid relative to total parabens.

Stability-indicating HPLC–DAD methods for determination of two binary mixtures: Rabeprazole sodium–mosapride citrate and rabeprazole sodium–itopride hydrochloride

“…DAD also supported the specificity of the method and provided evidence for the homogeneity of the peaks of analytes as the purity angles were always found much less than the threshold limit in all stressed samples. In addition, the observation that the wavelengths of derivative optima (first, second, third and fourth) of the spectrograms of the separated peaks obtained by chromatography of the test solutions were identical to those of corresponding standard was considered as evidence confirming the identity of the investigated compounds [28] , [29] . The derivative spectra were super-imposable whenever overlaid, showing that there were no other co-eluting peaks.…”

“…The derivative spectra were super-imposable whenever overlaid, showing that there were no other co-eluting peaks. Furthermore, the spectral homogeneity and purity of the peaks were confirmed using RA spectra and log A versus the wavelength plots [28] , [29] constructed from the data collected from the spectrograms of each peak. The superimpose of the relative absorption spectra and the traces of log A versus the wavelengths plots with those of corresponding standard for each peak proved the absence of interference as shown in Fig.…”

“…The spectral homogeneity and purity of the peaks due to the eluted RZ, MR and IO in their binary mixtures were also checked using the methods of relative absorption spectra (RA) and log A versus the wavelength plots. The absorption spectra (spectrograms) collected at different time intervals across the elution of the peaks of RZ, MR and IO were used to construct their RA spectra and log A versus λ plots [28] , [29] .…”