Simultaneous green TLC determination of nirmatrelvir and ritonavir in the pharmaceutical dosage form and spiked human plasma

Abstract

Quantitative analysis of pharmaceutical compounds up to Nano gram levels is highly recommended to introduce feasible and sensitive tool for determination of the compounds in the pharmaceutical and biological samples. Nirmatrelvir plus ritonavir was recently approved in the US, the UK and Europe as a new co-packaged dosage form for the treatment of COVID-19. The objective of this work was to develop a more sensitive TLC method based on using β-cyclodextrin as a chiral selector additive in the mobile phase for simultaneous determination of nirmatrelvir and ritonavir in pure form, pharmaceutical formulation and spiked human plasma. The analysis procedures were developed using TLC aluminum silica gel plates and methanol–water- 2% urea solution of β-cyclodextrin (40:10:.5, by volume) as a mobile phase with UV detection at 215 nm. The developed method was successfully applied over a linearity range of 10–50 ng/band for both nirmatrelvir and ritonavir. The method was validated for limits of detection and quantitation, accuracy, precision, specificity, system suitability, and robustness. Furthermore, the eco-friendliness of the proposed method was assessed using the analytical eco-scale and the green analytical procedure index. The described method exhibited compliance with green analytical chemistry principles based on common green metric values.

Recent analytical methodologies for the determination of anti-covid-19 drug therapies in various matrices: a critical review

“…Depending on the physical interaction between the drugs and the stationary phases the most appropriate stationary phase was C18 column (among C8, C18, Cyano column) and the most green and suitable mobile phase was ethanol : water (80 : 20, v/v) using the following equation. 53 Δ E = E A–B − E A − E B where A is the energy of the molecular structure of the nirmatrelvir or ritonavir, B is the energy of the molecular structure of column units and Δ E is the binding energy.…”

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

“…The scores were 0.95, 5 zeros/2 ones, and 99.6 using AGREE, hexagon, and RGB12 algorithms, respectively. Although the LC technique is controversial and swinging between the GAC and classical analytical chemistry using harmful solvents and producing a vast amount of waste, the results of the evaluation of the proposed method versus the cited ones 11–13 revealed the great tendency of the research groups to use green solvents and to downsize the residues. The collective Table 5 ranks the method in descending order according to their whiteness%.…”

“…However, the proposed HPLC offers a feasibility study for the stability of Paxlovid pills under different stress conditions. Concerning the HPTLC 13 and LC-Ms 11 reported methods, they still cover the green scope of analysis with AGREE SCORE (0.77, 0.66, respectively) and whiteness% (91.9, 91.1, respectively). The hexagon profile for both methods showed good green and sustainable performance with 4 zeros and 3 ones.…”

“…After reviewing the scientific databases meticulously, only three reported methods for the neat estimation of NMV and RIT in plasma and their co-packed tablet, namely LC-MS, HPLC-DAD, and HPTLC, respectively were found. 11–13 Regarding RIT, there are only two published capillary zone electrophoresis (CZE) methods for its separation either from other protease inhibitors 14 or from its impurities. 15 Furthermore, few LC methods dealing with the degradation studies of RIT were found.…”

Pharmacokinetic analysis of placental transfer of ritonavir as a component of paxlovid using microdialysis in pregnant rats

“…Different analytical methods have been developed to analyze ritonavir, including liquid chromatography coupled with photodiode array [ 26 ] or mass spectrometry [ [27] , [28] , [29] ]; thin layer chromatography [ 30 ], and spectrofluorometric detection [ 31 ]. For this experiment, ultra-high-performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS) was chosen for its good specificity and sensitivity, ease of new method development, and high throughput [ 32 ], at the same time allowing for less sample input compared to high performance liquid chromatography (HPLC).…”