Application of sustainable QbD based HPLC method for quantification of carboxylic-diphenyl methane drug ambrisentan loaded in solid lipid nanoparticles

Abstract

Background

The present study details the development and validation of a reverse-phase high-performance liquid chromatography method for quantifying ambrisentan in solid lipid-based nanocarriers, employing a Quality by Design methodology, along with assessments of greenness, blueness, and whiteness. A fractional factorial design was utilized to identify the key technique parameters affecting method development. The RP-HPLC process was systematically optimized using a Box-Behnken design.

Method

Chromatographic separation was performed using an isocratic flow system of acetonitrile and 1 % glacial acetic acid (39.5:60.5 v/v) on a Kromasil C18 column (4.6 × 100 mm, 5 μm) at a flow rate of 0.85 mL/min. The procedure was meticulously validated in accordance with ICH recommendations.

Results

Linearity was at a concentration range of 10–60 μg/mL, with a correlation coefficient of 0.999. The limits of detection and quantification were established at 0.04 μg/mL and 0.12 μg/mL, respectively. The established approach was utilized to quantify ambrisentan in formulated solid lipid nanocarriers. Recovery assays in lipid-based nanocarriers exhibited exceptional recovery rates (97.2–98.8 %). The proposed HPLC method secures a MoGAPI score of 80, AGREE score 0.82, BAGI score 70 and RGBFast 75.

Conclusion

The environmental sustainability of the suggested approach was assessed utilizing the White Analytical Chemistry framework, the Green Analytical Procedure Index, and AGREE. The approach received good scores in all assessments, validating its negligible environmental impact.