Development of a Novel Synchronous Spectrofluorimetric Method Coupled With Chemometric Modelling for Ultrasensitive Analysis of Tenofovir and Dolutegravir With Implication for Pharmacokinetic Studies

Abstract

This study introduces a novel synchronous spectrofluorimetry coupled with chemometric tools for the determination of tenofovir and dolutegravir antiretroviral drugs. Utilizing partial least squares regression (PLS) fine-tuned by genetic algorithm as variable selection tool, the developed models demonstrate greater sensitivity, cost-effectiveness, and reduced environmental impact compared to traditional HPLC methods. The model's validation was further confirmed using external validation in addition to QC samples as per ICH M10 guidelines, which yielded high accuracy ranged between 94.78% and 102.48% for tenofovir and 94.56% and 103.31% for dolutegravir, respectively. Additionally, the %CV values for within-run precision were below 4%, while those for between-run precision stayed under 6%, for tenofovir and dolutegravir, respectively. Hence, the developed models were adeptly applied to pharmacokinetic studies in a rat model, revealing slight changes in the tenofovir and dolutegravir plasma concentration profiles and half-lives when administered in combination, highlighting possible drug interactions. Greenness analysis of this spectrofluorimetric approach using the AGREE tool further substantiates its advantages over conventional chromatographic techniques. Hence, this simple, rapid, and environmentally friendly analytical methodology presents a promising alternative for therapeutic drug monitoring and pharmacokinetic studies of tenofovir and dolutegravir antiretroviral drugs.