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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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：Bempedoic酸（BEM）属于一类称为三磷酸腺苷-柠檬酸裂解酶（ACL）抑制剂的药物。它是口服给药的具有细胞内活化的前药。Bempedoicacid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，HPLC方法使用Kromasil100-5-C8柱（100mm×4.6mm），UV检测器设置在230纳米，和包含乙腈和0.1%正磷酸(OPA)缓冲液的70:30v/v混合物的流动相。该方法在环境温度下以1mL/min的流速操作。所开发的方法已根据ICH指南进行了统计验证。
结果:使用Kromasil100-5-C8(100mm×4.6mm)柱以1.0mL/min的流速进行稳定性指示方法。以70:30v/v比率的乙腈和0.1%正磷酸(OPA)缓冲液的混合物组成流动相。发现BEM的保留时间为每个1.88分钟。将温度保持在室温。234nm是BEM的理想波长。根据ICH标准，所开发的方法已经过统计验证。发现BEM的%RSD分别为0.6。对于BEM，%回收率确定为100.0%。bempedoic酸的回归模型得出的LoD和LoQ值为3.3和10.1g/mL，分别。该方法具有良好的重现性和回收率，RSD一%小于2。对强制降解的研究证实了该方法在应力条件下表明稳定性的能力，如酸，基本的，过氧化物,UV,热,和湿度。保留时间和运行时间均缩短。
结论：根据ICHQ2(R1)指南，用高效液相色谱法对该方法进行了测试，以确定新产生的bempedoic酸降解产物的化学结构。
方法：对于稳定性指示测定，HPLC方法使用Kromasil100-5-C8柱（100mm×4.6mm），UV检测器设置在230纳米，和包含乙腈和0.1%正磷酸(OPA)缓冲液的70:30v/v混合物的流动相。该方法在环境温度下以1mL/min的流速操作。所开发的方法已根据ICH指南进行了统计验证。
结果:使用Kromasil100-5-C8(100mm×4.6mm)柱以1.0mL/min的流速进行稳定性指示方法。以70:30v/v比率的乙腈和0.1%正磷酸(OPA)缓冲液的混合物组成流动相。发现BEM的保留时间为每个1.88分钟。将温度保持在室温。234nm是BEM的理想波长。根据ICH标准，所开发的方法已经过统计验证。发现BEM的%RSD分别为0.6。对于BEM，%回收率确定为100.0%。bempedoic酸的回归模型得出的LoD和LoQ值为3.3和10.1g/mL，分别。该方法具有良好的重现性和回收率，RSD一%小于2。对强制降解的研究证实了该方法在应力条件下表明稳定性的能力，如酸，基本的，过氧化物,UV,热,和湿度。保留时间和运行时间均缩短。
结论：根据ICHQ2(R1)指南，用高效液相色谱法对该方法进行了测试，以确定新产生的bempedoic酸降解产物的化学结构。
