Alshehri Adil, Alqahtani Ali, Alsayari Abdulrhman, Almrasy Ahmed A
Department of Medicine, College of Medicine, King Khalid University, 62529, Abha, Saudi Arabia.
Department of Pharmacology, College of Pharmacy, King Khalid University, 62529, Abha, Saudi Arabia.
BMC Chem. 2025 Jun 2;19(1):156. doi: 10.1186/s13065-025-01528-9.
This study develops and validates an eco-friendly ultraviolet (UV)-spectrophotometric method employing augmented least squares chemometric models for the simultaneous determination of three hepatitis C antiviral drugs-sofosbuvir, simeprevir, and ledipasvir. Two multivariate approaches were compared: Concentration Residual Augmented Classical Least Squares (CRACLS) and Spectral Residual Augmented Classical Least Squares (SRACLS). The experimental design utilized a 5-level partial factorial design for calibration (25 samples) and a central composite design for validation (20 samples). SRACLS models demonstrated superior analytical performance with lower detection limits (0.5171, 0.5175, 0.2950 μg/mL), higher precision (relative bias corrected mean square error of prediction, RBCMSEP: 0.1481-0.2509%), and better predictive capability (relative root mean square error of prediction, RRMSEP: 1.0285%, 1.2668%, 1.8933%) compared to CRACLS models (RRMSEP: 3.0655%, 1.9264%, 2.7201%). The SRACLS models also exhibited lower complexity with fewer principal components (3, 2, and 3) versus CRACLS iterations (4, 4, and 6). Application to commercial pharmaceuticals yielded excellent recoveries (99.70-100.39%) with no statistically significant difference from reference high-performance liquid chromatography (HPLC) methods. Greenness assessment confirmed the method's environmental advantages with superior scores in multiple sustainability metrics (Analytical GREEnness metric, AGREE: 0.75; Modified Green Analytical Procedure Index, MOGAPI: 78; RGB12 whiteness score: 94.2) compared to conventional chromatographic techniques (AGREE: 0.63-0.65, MOGAPI: 66-72, RGB12: 76.9-83.3). These findings establish the proposed method as a rapid, sensitive, and eco-friendly alternative for routine quality control of these critical hepatitis C drugs.
本研究开发并验证了一种采用增强最小二乘法化学计量学模型同时测定三种丙型肝炎抗病毒药物——索磷布韦、西米普明和来迪帕司韦的环保型紫外分光光度法。比较了两种多元方法：浓度残差增强经典最小二乘法（CRACLS）和光谱残差增强经典最小二乘法（SRACLS）。实验设计采用5水平部分因子设计进行校准（25个样品），并采用中心复合设计进行验证（20个样品）。与CRACLS模型（预测相对均方根误差，RRMSEP：3.0655%、1.9264%、2.7201%）相比，SRACLS模型表现出更好的分析性能，具有更低的检测限（0.5171、0.5175、0.2950μg/mL）、更高的精密度（预测相对偏差校正均方误差，RBCMSEP：0.1481 - 0.2509%）和更好的预测能力（RRMSEP：1.0285%、1.2668%、1.8933%）。与CRACLS迭代次数（4、4和6）相比，SRACLS模型还表现出更低的复杂性，主成分更少（3、2和3）。应用于市售药品时，回收率极佳（99.70 - 100.39%），与参考高效液相色谱（HPLC）方法相比无统计学显著差异。绿色度评估证实了该方法的环境优势，在多个可持续性指标上得分更高（分析绿色度指标，AGREE：0.75；改进的绿色分析程序指数，MOGAPI：78；RGB12白度得分：94.2），相比传统色谱技术（AGREE：0.63 - 0.65，MOGAPI：66 - 72，RGB12：76.9 - 83.3）。这些发现确立了所提出的方法作为这些关键丙型肝炎药物常规质量控制的快速、灵敏且环保的替代方法。
