Tambare Rashmi S, Shahi Sadhana R, Gurumukhi Vishal C, Kakade Suhas M, Tapadiya Ganesh G
Department of Pharmaceutics, Shreeyash Institute of Pharmaceutical Education and Research, Aurangabad, 431010, Maharashtra, India.
Department of Pharmaceutics, Government College of Pharmacy, Aurangabad, 431001, Maharashtra, India.
Heliyon. 2024 Oct 10;10(20):e39172. doi: 10.1016/j.heliyon.2024.e39172. eCollection 2024 Oct 30.
Buserelin acetate (BA) is the first gonadotropin hormone to reduce the level of estrogen for the treatment of breast cancer. In the present study, RP-HPLC study has been developed and validated subsequently using the analytical quality by design (AQbD) approach. Initially, an analytical target profile (ATP) was defined that outlined the performance of the established method. The risk identification and its assessment were performed using the Ishikawa fishbone diagram and risk assessment method (RAM) to identify critical method parameters (CMPs) having influence on critical analytical attributes (CAAs). The flow rate and pH of buffer were identified as CMPs and retention time (Rt) and peak area (Pa) were recognized as CAAs. The optimization of the method was determined by response surface methodology based on central composite design (CCD). The chromatographic separation was achieved by mobile phase (water: acetonitrile, 80:20 %, v/v) and pH was adjusted using orthophosphoric acid with Zorbax Eclipse plus C18 (4.6 mm × 150 mm × 5 μm) column. Elution was monitored at 220 nm using a photodiode array (PDA) detector. The calibration curve showed the linearity (regression coefficient, R = 0.9991) over the concentration range of 10-60 μg/mL. The limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.051 μg/mLand 0.254 μg/mL respectively. The method for analysis of BA was accurate using recovery ranging from 100.55 ± 0.93 to 103.45 ± 0.32 whereas the method was precise with % RSD for all parameters of chromatographic system was found to be not more than 1.0 %. Further, the method was robust based on intentionally changing the chromatographic conditions according to the recommended ICH Q2 (R1). Furthermore, poly D, L-lactic-co-glycolic (PLGA- Resomer RG505 and Resomer RG750) (50:50) based nanoparticles were prepared to encapsulate BA and understand the release of BA over the period of 48 h with Korsmeyer-Peppas release kinetics model. The stability of the stock solution was assessed over the 8th day and found to be stable for a longer duration of time. The method has been successfully applied for the analysis of BA in polymeric nanoparticles.
醋酸布舍瑞林（BA）是第一种用于降低雌激素水平以治疗乳腺癌的促性腺激素。在本研究中，随后采用设计分析质量（AQbD）方法开发并验证了反相高效液相色谱（RP-HPLC）研究。最初，定义了一个分析目标概况（ATP），概述了既定方法的性能。使用石川鱼骨图和风险评估方法（RAM）进行风险识别及其评估，以识别对关键分析属性（CAA）有影响的关键方法参数（CMP）。缓冲液的流速和pH被确定为CMP，保留时间（Rt）和峰面积（Pa）被视为CAA。基于中心复合设计（CCD）的响应面方法确定了方法的优化。通过流动相（水：乙腈，80:20%，v/v）实现色谱分离，使用正磷酸调节pH，采用Zorbax Eclipse plus C18（4.6 mm×150 mm×5μm）色谱柱。使用光电二极管阵列（PDA）检测器在220 nm处监测洗脱。校准曲线在10 - 60μg/mL的浓度范围内显示出线性（回归系数，R = 0.9991）。检测限（LOD）和定量限（LOQ）分别为0.051μg/mL和0.254μg/mL。BA的分析方法准确，回收率在100.55±0.93至103.45±0.32之间，而该方法精密，色谱系统所有参数的相对标准偏差（%RSD）不超过1.0%。此外，根据推荐的国际协调会议（ICH）Q2（R1）故意改变色谱条件，该方法具有稳健性。此外，制备了基于聚D，L-乳酸-乙醇酸共聚物（PLGA-Resomer RG505和Resomer RG750）（50:50）的纳米颗粒来包封BA，并使用Korsmeyer-Peppas释放动力学模型了解BA在48小时内的释放情况。储备溶液在第8天进行了稳定性评估，发现其在较长时间内稳定。该方法已成功应用于聚合物纳米颗粒中BA的分析。
