ABSTRACT
As long as the COVID-19 pandemic is not over, Pfizer had launched the novel pills Paxlovid® (Nirmatrelvir (NMV) co-packaged with Ritonavir (RIT)) as an effective medication for hospitalized and non-hospitalized patients. Making pharmaceutical analysis greener and more sustainable is lately the main direction of the research community. In these contexts, two fast, green and stability indicating chromatographic methods were designed for the neat quantitative determination of NMV and RIT in their bulk and dosage forms. Method I is deemed as the first electro-driven attempt for the assay of Paxlovid®. Herein, the optimized conditions of the Micellar Electrokinetic Chromatographic (MEKC) method was 50 mM borate buffer at pH 9.2 with 25 mM sodium lauryl sulfate (SDS) being used as the back ground electrolyte (BGE) on a deactivated fused silica capillary (50 cm effective length × 50 μm id). Method II was an isocratic reversed phase HPLC separation method using Zorbax-Eclipse C18 (4.6 × 250 mm, 5 μm particle size) column and 50 mM ammonium acetate buffer at pH 5 and acetonitrile as mobile phase constituents at flow rate 1 mL/min. For sake of simplicity and increasing the sensitivity, single wavelength 210 nm was used for the two methods to assay both drugs. Linear correlations between peak areas and concentration were observed in the ranges of 10–200 μg/mL for NMV and 5–100 μg/mL RIT in both methods. The impact of versatile stress conditions such as hydrolysis, oxidation and photolysis on the stability of NMV and RIT were studied. Fortunately, both methodologies were capable to separate both drugs from their degradants. Thus, the stability indicating power of the methods were proved. The derived methods were statistically validated in agreement with the ICH guidelines. Furthermore, the environmental friendliness and sustainability of these methods were investigated and compared with the cited methods using the holistic multicriteria evaluation tools namely Hexagon, AGREE and RGB12 Methods. Conclusively, the proposed methods offered reliable, feasible, economic, white and stability-indicating alternatives to the cited chromatographic methods.