Development and Validation of a Stability-Indicating RP-HPLC Method for the Simultaneous Estimation of Guaifenesin and Dextromethorphan Impurities in Pharmaceutical Formulations
A sensitive, stability-indicating gradient RP-HPLC method has been developed for the simultaneous estimation of impurities of Guaifenesin and Dextromethorphan in pharmaceutical formulations. Efficient chromatographic separation was achieved on a Sunfire C18, 250？×？4.6？mm, 5？μm column with mobile phase containing a gradient mixture of solvents A and B. The flow rate of the mobile phase was 0.8？mL min？1 with column temperature of 50°C and detection wavelength at 224？nm. Regression analysis showed an r value (correlation coefficient) greater than 0.999 for Guaifenesin, Dextromethorphan, and their impurities. Guaifenesin and Dextromethorphan formulation sample was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Guaifenesin was found stable and Dextromethorphan was found to degrade significantly in peroxide stress condition. The degradation products were well resolved from Guaifenesin, Dextromethorphan, and their impurities. The peak purity test results confirmed that the Guaifenesin and Dextromethorphan peak was homogenous and pure in all stress samples and the mass balance was found to be more than 98%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines with respect to specificity, linearity, limits of detection and quantification, accuracy, precision, and robustness. 1. Introduction Guaifenesin (GN), (+)-3-(2-methoxyphenoxy)-propane-1,2-diol, is a widely used expectorant, useful for the symptomatic relief of respiratory conditions. Its empirical formula is C10H14O4, which corresponds to a molecular weight of 198.21. It is a white or slightly gray crystalline substance with a slightly bitter aromatic taste. Its solid oral dosage form is available as extended release tablets for oral administration [1]. Dextromethorphan (DN) [2–4] is the dextrorotatory enantiomer of the methyl ether of？？levorphanol and stereoisomer of levomethorphan. DN is an antitussive (cough suppressant) drug and used for pain relief and psychological applications [5–7]. Its empirical formula is C8H25NO, which corresponds to a molecular weight of 271.4. It is a white powder. The combination of GN and DN is used to treat cough and chest congestion caused by the common cold, infections, or allergies. The chemical structures of GN and DN are shown in Table 1. Table 1: Structures of Guaifenesin and Dextromethorphan. Impurity profiling of active pharmaceutical ingredients (API) in both bulk material and finalized formulations is one of the most challenging tasks
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