Advances in Pharmacoepidemiology and Drug Safety

Bioanalytical method development, validation and pharmacokinetics study of 5-fluorouracil loaded nanoparticles

11^th International Conference on Pharmacoepidemiology and Clinical Research

October 02-03, 2017 Kuala Lumpur, Malaysia

Saurabh Srivastava

King George�??s Medical University, India

Posters & Accepted Abstracts: Adv Pharmacoepidemiol Drug Saf

Abstract:

Background: 5-fluorouracil (5FU) is a chemotherapeutic agent against different types of cancer. 5FU loaded with nanotechnology can enhance efficacy over conventional drawback of 5-FU, such as short half-life, toxicity, low bioavailability and non-selective action. Pharmacokinetic profile of this advanced nano-formulation is needed to correlate with overall ADME (absorption, distribution, metabolism and excretion) process. Aim: The purpose of this study is to develop HPLC-UV method and validate the performance in expression of specificity, precision, sensitivity, accuracy and stability of the developed 5-fluorouracil nanoparticles (5-FUNPs) and to correlate and collect the valuable pharmacokinetics data. Methodology: 5-FUNPs were formulated with polymer poly lactic co-glycolic acid with oil-in-water/solvent evaporation. Characterizations of nanoformulation was performed which included particle size and stability studies. Analytical method was developed and validated from HPLC-UV and was applied to pharmacokinetic parameters. Results: The calibration curve plotted for 5-FUNPs was linear at 267 nm. The lower limit for the quantification was found 10.13 ng/mL. The size of 5-FUNPs was between 137±0.97 to 193±0.93 nm and zeta potential between 0.27±0.08 to 0.29±0.07 mv on the side of positively charged. The highest peak for drug concentration, Cmax was 3.235±0.78 mg/L at highest time point, Tmax 7.21±2.52 hours. The AUC(0-96) and AUC(0-�??) showed 8.89±4.98 mg/L-h and 9.57±3.77 mg/L-h respectively and t1/2 was 22.98±3.73 hours. Conclusion: The results showed a simple, specific, sensitive and stable HPLC-UV method for the quantitative determination of 5-FUNPs in plasma and successfully applied to the pharmacokinetic study after oral administration in rats.