Tailoring two white chromatographic platforms for simultaneous estimation of ritonavir-boosted nirmatrelvir in their novel pills: degradation, validation, and environmental impact studies.

Abstract

As the COVID-19 pandemic is not yet over, Pfizer has launched the novel pill 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 has lately become the main direction of the research community. In this context, 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 the first electro-driven attempt for the assay of Paxlovid®. Herein, the optimized conditions of the Micellar Electrokinetic Chromatographic (MEKC) method were 50 mM borate buffer at pH 9.2 with 25 mM sodium lauryl sulfate (SDS) being used as the background 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 a flow rate of 1 mL min-1. For the sake of simplicity and increasing sensitivity, a single wavelength of 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-1 for NMV and 5-100 μg mL-1 RIT in both methods. The impact of versatile stress conditions such as hydrolysis, oxidation, and photolysis on the stability of NMV and RIT was studied. Fortunately, both methodologies were able to separate both drugs from their degradants. Thus, the stability indicating power of the methods was 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 metrics. Conclusively, the proposed methods offered reliable, feasible, economic, white, and stability-indicating alternatives to the cited chromatographic methods.