Physico-Chemical Stability of Mixtures of Fosaprepitant used in Clinical Practice
Maria Amparo Martínez-Gómez
Journal of Analytical & Bioanalytical Techniques
Fosaprepitant dimeglumine is a new drug indicated to prevent nausea and vomiting associated with highly emetogenic cisplatin-based and moderately emetogenic cancer chemotherapy in adults. Due to its complexity in managing, since it requires reconstitution and dilution before intraveonous administration, it is necessary to evaluate physico-chemical stability of fosaprepitant at concentrations used in our routine clinical practice and at different conditions of storage to expand the information
... tasheet (fosaprepitant 150 mg in 150 mL of 0.9 g/dl sodium chloride (NaCl) at ambient conditions and light for 24 hours) and simplify preparation technique conforming to the fluid marketed branches. These studies should be carried out following the recommendations International Conference on Harmonisation (ICH) guidelines for evaluate stability and the criteria of the United States Pharmacopeia to maintain quality and safety of the preparation. So, stability study of fosaprepitant 150 mg in 50, 100 and 250 mL of 0.9 g/dl NaCl at room temperature/refrigerated and protective from/exposed to ambient light has been carried out. An HPLC method has been developed and validated according to ICH guidelines to evaluate chemical stability of fosaprepitant. Physical stability study has been carried out by visual inspection, measure of pH and gravimetry to control evaporation. The results shown in this paper represent the first evidence of the physico-chemical stability of the mixtures of fosaprepitant 150 mg in 50, 100 and 250 mL of 0.9 g/dl NaCl are physico-chemically stable for 7 days at room temperature (27.0 ± 0.9°C) and refrigerated (4.9 ± 1.5°C); and exposed to ambient light, 15 days at room temperature and refrigerated and protected from light and 12 days fosaprepitant reconstituted and stored refrigerated and exposed to light. The developed chromatographic method was validated for linearity, specificity, accuracy, precision, limit of detection, limit of quantification and robustness as per ICH guidelines [9, 10] . The chromatograms were evaluated on the basis of the peak area of FOS. Linearity: The linearity was determined at six levels of FOS over the range 0.15-3.9 mg/mL. Absorbance of each calibrator was measured and the graph mean absorbance (y-axis) versus concentration (x-axis) was plotted. Correlation coefficient (r), y-intercept and slope of regression line were estimated. Specificity: The specificity of the method was ascertained by evaluating the presence of interferences at the retention time of FOS. Accuracy (% Recovery): The accuracy of the method was determined by calculating recoveries of FOS by method of standard additions. Known amount of FOS (0%, 50%, 100%, 150%) were added to a pre quantified sample solution, and the amount of FOS was estimated by measuring the peak areas and by fitting these values to the straight-line equation of calibration curve. Method precision (Repeatability): Standard solutions of FOS (0.15, 1.50 and 3.00 mg/mL) were analyzed six times and relative standard deviation (%RSD) was calculated for each concentration level.