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

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 70:30 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 70:30 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.

Analytical Method Development, Validation and Forced Degradation Study of Dapagliflozin by RP-HPLC.

BACKGROUND: Worldwide, it is projected that 285 million individuals have diabetes, and by 2030, this number is expected to climb to 438 million. About 90% of cases of diabetes mellitus are type 2 (T2DM). Insulin sensitizers, such as metformin and thiazolidinediones; insulin secretagogues, such as sulfonylureas and glinides; dipeptidyl peptidase 4 (DPP-4) inhibitors; glucosidase inhibitors, or oral combination therapy are currently available treatments for type 2 diabetes. Some of these drugs exhibit serious limitations; thus, it is crucial to design an innovative therapy that is efficient and depends on a new channel. AIM: In the current work, a stability-indicating reverse phase HPLC (RP-HPLC) technique was developed and subsequently validated for the detection of dapagliflozin in its API. METHODS: The stability-indicating HPLC method for assay included the use of Kromasil 100-5-C8 (100 mm × 4.6 mm) column, UV detector 224 nm, mobile phase composition involving a mixture of acetonitrile:water (52:48), and a flow rate of 1.0 mL/min. ICH guidelines were followed for the method's validation. To assess the method's specificity and stability in showing characteristics, stress degradation studies were carried out. The working standard solution of dapagliflozin was exposed to 1 and 2 N HCl by refluxing 1 and 2 N NaOH with 30% hydrogen peroxide by volume and UV radiation in order to conduct a degradation study. RESULTS: All system suitability parameters were determined to be within the intended ranges, and the drug's retention duration was discovered to be 1.67 minutes. It was also investigated as to how the drug degraded under various circumstances. The drug was discovered to be stable under situations of photolytic, thermal, neutral, alkaline, and oxidative deterioration. The developed stabilityindicating HPLC technique was validated in accordance with ICH Q2 recommendations, and the validation parameters, such as linearity, precision, and robustness, were achieved within the approved standards. CONCLUSION: It may be concluded that this method is stability-indicating and specific, and it can be successfully applied to analyze tablet dosage forms containing dapagliflozin.