Objective: The main objective of this research is to develop and validate a simple, specific, precise, sensitive, cost-effective, and rapid reversed-phase high-performance liquid chromatography method for simultaneous quantification of glucosamine (GLU), diacerein (DIA) and methyl sulfonyl methane in bulk and pharmaceutical dosage forms, and micro-sample of rat plasma using ultraviolet (UV) detection, to perform the studies of drug dissolution from tablets. Methods: Sprague-Dawley rats were used for pharmacokinetic study after intravenous administration of the drug samples at dose 5 mg/kg. The drug samples were extracted by liquid-liquid extraction technique using acetonitrile, which also acted as a deproteinization agent. The separation of the analyte was carried out on a phenomena C18 column with a mobile phase composed of 0.1 % orthophosphoric acid:acetonitrile (80:20 v/v) delivered at a flow rate of 1.0 ml/min, and separation has been monitored by a UV detector, at detection of the wavelength of 285 nm. Results: This method was proven to be linear over a concentration range of 30–450 μg/ml for GLU, 2–30 μg/ml for DIA, and 10–150 μg/ml for methyl sulfonyl methane with a correlation coefficient of 0.999. The retention time of GLU, DIA, and methyl sulfonyl methane were 2.89, 6.32, and 9.87 min, respectively. Recovery of the drugs was found to be in the range of 98.0–102.0%. Validation results were found to be satisfactory and the method applicable for bulk and formulation analysis. Hence, it was evident that the proposed method was said to be a suitable one for the regular analysis and quality control of pharmaceutical preparations which contain these active drugs either individually or in combination. Conclusion: The validation results were in good agreement with acceptable limits. Relative standard deviation values which are less than 2.0% are indicating the accuracy and precision of this method. The usefulness of the method is that the common chromatographic conditions have been adopted for assay, dissolution, and pharmacokinetic studies. This developed method showed reliable, precise, and accurate results under optimized conditions.

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Podili et al.: Estimation of Related Substances, Assay of Cabozantinib and Nivolumab and its Application to Dissolution StudiesThe present work describes the development and subsequent validation of a novel, simple, selective and stability indicating gradient reversed phase high performance liquid chromatography method for the quantitative determination of related substances, assay of cabozantinib and nivolumab and its application to dissolution studies. The chromatographic method was optimized using the impurity-spiked solution. A good resolution between the peaks was achieved under selected chromatographic conditions. The separation was accomplished on an X-Bridge C18, 150×4.6 mm, 3.5 µ column connected to a photo diode array detector using 0.1 % orthophosphoric acid in water as mobile phase A and acetonitrile as mobile phase B, under gradient elution. The mobile phase flow rate was maintained at 1.0 ml/min. The detection of the constituents was done at 216 nm using a ultra-violet detector. Recovery studies were satisfactory and the correlation coefficient for two active pharmaceutical ingredients and their related substances, 0.999 indicates the linearity of the method within the limits. Limit of detection and limit of quantification for all impurities and cabozantinib and nivolumab were established with respect to the test concentration. Specificity, accuracy, precision, ruggedness and robustness were determined as part of the method validation. The performance of the method was validated according to the current International Council for Harmonisation requirements. Moreover, the dissolution study was performed on active pharmaceutical ingredients to estimate the recovery using the same method. Validation of the developed reversed phase high performance liquid chromatography procedure revealed that all the degradation products formed during stress conditions and related impurities were well separated from their active pharmaceutical ingredients and peaks were well resolved from each other with appropriate retention time. The method was characterized by good linearity, specificity, low values of limit of detection and quantisation, accuracy, precision, ruggedness and robustness. All statistical results were within the acceptance criteria and the proposed method is simple, fast, accurate, precise and reproducible hence, it can be applied for routine dissolution analysis and employed for quality control of drug samples during stability studies.