Development and Validation of a Robust HPLC Method for Simultaneous Estimation of 5-Fluorouracil and Resveratrol and its Application in the Engineered Nanostructured Lipid Carrier

Abstract

Background: 5-fluorouracil and resveratrol are the two most effective anticancer drugs. Combination therapy with these two drugs has shown promising results in cancer. The formulation containing 5-fluorouracil and resveratrol has been prepared, but no analytical method is available in the literature for their simultaneous estimation. However, several analytical methods are there for estimation of either 5-fluorouracil or resveratrol alone. Therefore, the present article is designed for the simultaneous estimation of 5-fluorouracil and resveratrol by HPLC and its application in the quantification of the drugs present in the formulated nanostructured lipid carrier (NLC). Methods: The method was developed using a C18 column (Purospher® STAR RP-18 endcapped (5 µm) Hibar® RT 250- 4.6) with acetonitrile and water as the mobile phase (25:75 v/v) and estimated at 272 nm. The currently developed method was further validated by the ICH guideline Q2 (R1). Combinatorial NLC of 5-fluorouracil and resveratrol was also prepared and characterized. Results: The LOD and LOQ were 8.22 and 24.91 µg mL-1 and 6.58 and 19.93 µg mL-1 , respectively. The precisions was under the acceptable limits of < 2% RSD. The content of 5-fluorouracil and resveratrol in NLC were found to be 65.558±1.343% and 96.326±1.421%, respectively. Conclusion: The findings showed that the developed and validated method was simple, fast, cost-effective and reproducible for the simultaneous estimation of both the drugs in the same formulation.

HSPiP, Computational Modeling, and QbD-Assisted Optimized Method Validation of 5-Fluorouracil for Transdermal Products

“…This may be prudent to correlate with the hydrogen bond donor counts and hydrogen bond acceptor counts of the drug with solvent (as shown in Figure A–D). Figure A,B depicts the chemical structure of the drug (the site of hydrogen bond interaction) and the reported cocrystal formation of the drug with urea, aspirin, and acetanilide. , Figure C depicts a detailed SAR (structure–activity relationship), whereas Figure D illustrates various physicochemical properties and pharmacokinetic parameters of the drug. , Conclusively, the maximum content of water in the “acetonitrile + water” combination to achieve RED < 1.0 could be 25% as predicted in the program. Thus, the optimized composition of the mixture for maximum solubility of the drug could be acetonitrile with 75–96%.…”

“…Figure 1A,B depicts the chemical structure of the drug (the site of hydrogen bond interaction) and the reported cocrystal formation of the drug with urea, aspirin, and acetanilide. 30,31 Figure 1C depicts a detailed SAR (structure−activity relationship), whereas Figure 1D illustrates various physicochemical properties and pharmacokinetic parameters of the drug. 30,31 Conclusively, the maximum content of water in the "acetonitrile + water" combination to achieve RED < 1.0 could be 25% as predicted in the program.…”

“…30,31 Figure 1C depicts a detailed SAR (structure−activity relationship), whereas Figure 1D illustrates various physicochemical properties and pharmacokinetic parameters of the drug. 30,31 Conclusively, the maximum content of water in the "acetonitrile + water" combination to achieve RED < 1.0 could be 25% as predicted in the program. Thus, the optimized composition of the mixture for maximum solubility of the drug could be acetonitrile with 75−96%.…”

“…The prediction is in good agreement with the published report where Iqubal et al employed a 75:25 ratio of acetonitrile and water for HPLC-based method validation of analysis. 30 However, the predicted ratio needs to be revalidated to corroborate the tangible interaction-based solubilization in the predicted combination by comparison with the experimental solubility data. The anticancer potential of the drug depends upon the ability of the drug capable of being taken up by the targeted cells.…”

“…Thus, the optimized composition of the mixture for maximum solubility of the drug could be acetonitrile with 75–96%. The prediction is in good agreement with the published report where Iqubal et al employed a 75:25 ratio of acetonitrile and water for HPLC-based method validation of analysis . However, the predicted ratio needs to be revalidated to corroborate the tangible interaction-based solubilization in the predicted combination by comparison with the experimental solubility data.…”