Abstract
A sensitive, stability-indicating, gradient reversed-phase ultra-performance liquid chromatography method has been developed for the quantitative estimation of cinacalcet hydrochloride impurities in active pharmaceutical ingredients and pharmaceutical formulations. Efficient chromatographic separation was achieved on an Acquity BEH Shield RP18, 100 × 2.1 mm, 1.7 µm column with the mobile phase containing pH 6.6 phosphate buffer and acetonitrile. The flow rate of the mobile phase was 0.3 mL min−1 with a column temperature of 35°C and detection wavelength at 223 nm. The relative response factor values of (+)-R-1-(1-Naphthyl)ethylamine, regioisomer, diastereomer isomer-1, and diastereomer isomer-2 were 1.79, 0.99, 0.89, and 0.88, respectively. The cinacalcet hydrochloride formulation sample was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal, humidity, and photolytic degradation. Cinacalcet hydrochloride was found to degrade significantly under the peroxide stress conditions. The degradation products were well-resolved from cinacalcet hydrochloride and its impurities. The peak purity test results confirmed that the cinacalcet hydrochloride peak was homogenous in all stress samples and the mass balance was found to be more than 96%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines.
Highlights
Cinacalcet hydrochloride (CH) is an oral calcimimetic indicated for the treatment of secondary hyperparathyroidism (HPT) in patients on dialysis with end-stage renal disease (ESRD), and in patients with parathyroid carcinoma to reduce hypercalcemia
Stability of the Sample Solution and Stability of the Mobile Phase CH-spiked samples were prepared in the diluent and the test solutions were left at room temperature
Individual stock solutions of CH and its impurities of same concentrations were scanned in a photodiode array detector in the range of 200 to 400 nm and the spectra of each component was checked
Summary
Cinacalcet hydrochloride (CH) is an oral calcimimetic indicated for the treatment of secondary hyperparathyroidism (HPT) in patients on dialysis with end-stage renal disease (ESRD), and in patients with parathyroid carcinoma to reduce hypercalcemia. Development and Validation of a Stability-Indicating RP-UPLC Method for the Estimation of Impurities ...585. The presence of unwanted, or in certain cases unknown chemicals, even in small amounts, may influence the therapeutic efficacy, and the safety of the pharmaceutical products [10] For these reasons, International Conference Harmonization guidelines have established maximum allowed limits for related compounds for both bulk and formulated APIs. As per the requirements of various regulatory authorities, the impurity profile study of drug substances and drug products has to be carried out using a suitable analytical method in the final product [11, 12]. The impurity stock solutions (100 μg mL−1) were prepared in diluent. The supernatant (550 μg mL−1 of CH) was collected, filtered through a 0.22 μ filter, and used as sample solution
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