反相高效液相色谱法测定贝匹地酸的稳定性指示方法开发与验证。

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

机构信息

Department of Pharmaceutical Quality Assurance, School of Pharmacy & Technology Management, SVKM's NMIMS (Deemed to be University), Shirpur, Distt - Dhule, Maharashtra, 425405, India.

Department of Pharmacy, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura (W), 799022, India.

出版信息

Drug Metab Bioanal Lett. 2024;17(1):23-33. doi: 10.2174/0118723128278080240404052506.

DOI:10.2174/0118723128278080240404052506

PMID:38994699

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 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.

摘要

背景

贝匹地酸（BEM）属于三磷酸腺苷-柠檬酸裂解酶（ACL）抑制剂类药物。它是一种具有细胞内激活作用的前药，口服给药。贝匹地酸用于治疗现有的动脉粥样硬化性心血管疾病，主要是高胆固醇血症。

方法

对于稳定性指示测定，采用 HPLC 法，使用 Kromasil 100-5-C8 柱（100mm×4.6mm），UV 检测器设置在 230nm，流动相由乙腈和 0.1%正磷酸（OPA）缓冲液的 70:30v/v 混合物组成。方法在环境温度下操作，流速为 1mL/min。所开发的方法已根据 ICH 指南进行了统计学验证。

结果

使用 Kromasil 100-5-C8（100mm×4.6mm）柱以 1.0mL/min 的流速执行稳定性指示方法。流动相由乙腈和 0.1%正磷酸（OPA）缓冲液的 70:30v/v 混合物组成。贝匹地酸的保留时间分别为 1.88 分钟。温度保持在室温。BEM 的理想波长为 234nm。根据 ICH 标准，所开发的方法已经过统计学验证。贝匹地酸的%RSD 分别为 0.6。对于 BEM，回收率确定为 100.0%。贝匹地酸的回归模型得到的检测限（LoD）和定量限（LoQ）分别为 3.3 和 10.1μg/mL。该方法显示出良好的重现性和回收率，其%RSD 小于 2。强制降解研究证实，该方法能够在酸、碱性、过氧化物、UV、热和湿度等应激条件下指示稳定性。保留时间和运行时间都缩短了。