An Antiviral Drug-Peramivir: Degradation and Identification of Impurities and the Endorsement of an HPLC-MS Method.

BACKGROUND: Peramivir is a neuraminidase inhibitor that serves as a transition state analogue for influenza neuraminidase, inhibiting the formation of new viruses in infected cells, and has been approved for intravenous administration. OBJECTIVE: To validate an HPLC method used to identify the degraded products of the antiviral drug peramivir. METHODS: Herein, we report the identification of compounds formed after the degradation of peramivir through acid, alkali, peroxide, thermal, and photolytic degradation. At the level of toxicology, a technique was devised for the isolation and measurement of peramivir. RESULTS: A sensitive and reliable LC-tandem mass spectrometry technique for the quantitative measurement of Peramivir and its impurities was developed and verified in order to comply with the recommendations made by the International Council for Harmonisation (ICH). The proposed protocol was in the 50-750 µg/mL range. Relative Standard Deviation values of less than 2.0% indicated good recovery in the range of 98.36-102.57%. Within the studied range, the calibration curves demonstrated good linearity and, in addition, the fitting of correlation coefficient was more than 0.999 for every impurity. Quantitative analysis of contaminants revealed the high efficiency at a low level. CONCLUSION: Given its ability to separate degradation products, quantitative analysis is used to detect and quantify known and unknown impurities and degradants in the peramivir drug substance during routine analysis and stability studies. No significant degradation was found in peroxide and photolytic degradation studies. HIGHLIGHTS: An HPLC method was developed and put to the test in order to analyze the behavior of the impurities of peramivir as they degraded when subjected to the stress conditions suggested by the ICH. Peramivir was found to be stable under peroxide and photolysis conditions but not stable or degradable when exposed to the acid, base, and thermal stress conditions. The method developed was extremely precise, linear, accurate, robust, and rugged. As a result, this technology has the potential to be used in the medication production process for regular impurity analysis as well as for the stability analysis of peramivir.

Stability-Indicating RP-HPLC Method Development and Validation for Eltrombopag Olamine in the Presence of Impurities and Degradation Products. Robustness by Design of Expert Software.

BACKGROUND: A simple and reliable HPLC method for determining impurities in eltrombopag olamine (ELO) film-coated tablets is not available. At the same time, there is no official monograph reported. The proposed research is targeted at the development of a stability-indicating method for determining impurities in ELO film-coated tablets and drug substances. OBJECTIVE: To develop and validate a simple and effective HPLC method for determining impurities in ELO film-coated tablets and drug substances. METHODS: All the impurities were separated using a reverse phase (RP)-HPLC system equipped with a Zorbax SB-Phenyl 150 mm × 4.6 mm, 3.5 µm, column with UV detection at 230 nm and a flow rate of 1.2 mL/min. The column temperature was maintained at 45°C. RESULTS: The proposed method was validated as per current regulatory guidelines. The coefficient of correlation was found to be >0.999 for all impurities. The LOD and LOQ for ELO and all specified impurities were determined. The precision and accuracy were obtained for ELO and its related impurities. Intra- and inter-day RSD values were between 1.22 and 2.04%, and impurity recovery varied between 93.80 and 103.69%. The stability of standard and sample solutions was established for 24 h. CONCLUSIONS: As per recent guidelines, a stability-indicating method has been developed to determine the impurities in ELO film-coated tablets and drug substances. QbD-based robustness was performed and proved that the method was robust. HIGHLIGHTS: The proposed article is the first RP-HPLC method for determining impurities in ELO film-coated tablets and drug substances. The quality by design (QbD) concept was utilized to verify the method performance.