Stability Indicating Method Development and Validation for the Estimation of Bempedoic Acid by RP-HPLC.

ABSTRACT

BACKGROUND: Bempedoic acid (BEM) belongs to a category of drugs known as Adenosine triphosphate-citrate Lyase (ACL) inhibitors. It is a prodrug with intracellular activation that is administered orally. Bempedoic acid is used to treat existing atherosclerotic cardiovascular diseases, mainly hypercholesterolemia. METHODS: For the stability-indicating assay, the HPLC method was employed using a Kromasil 100-5-C8 column (100 mm × 4.6 mm), a UV detector set at 230 nm, and a mobile phase comprising a 7030 v/v mixture of acetonitrile and 0.1% Orthophosphoric Acid (OPA) buffer. The method was operated at an ambient temperature with a flow rate of 1 mL/min. The method developed has been statistically validated according to ICH guidelines. RESULTS: The stability-indicating method was executed using a Kromasil 100-5-C8 (100 mm × 4.6 mm) column at a 1.0 mL/min flow rate. A mixture of acetonitrile and 0.1% Orthophosphoric Acid (OPA) buffer in a 7030 v/v ratio made up the mobile phase. BEM's retention times were discovered to be 1.88 minutes each. The temperature was kept at room temperature. 234 nm was the ideal wavelength for BEM. According to ICH criteria, the approach developed has undergone statistical validation. BEM's % RSD was discovered to be 0.6, respectively. For BEM, the % recovery was determined to be 100.0%. Regression models for bempedoic acid yielded LoD and LoQ values of 3.3 and 10.1 g/mL, respectively. The method showed good reproducibility and recovery with a % RSD less than 2. Studies on forced degradation confirmed the method's capacity to indicate stability in the presence of stress conditions, such as acid, basic, peroxide, UV, heat, and humidity. Both the retention times and the run time were shortened. CONCLUSION: In accordance with ICH Q2 (R1) guidelines, this method was successfully tested with HPLC to confirm the chemical structures of newly produced degradation products of bempedoic acid.