洛伐他汀有关物质HPLC分析方法的优化

目的: 按质量源于设计(Q_bD)的理念,采用实验设计的方法,优化洛伐他汀有关物质的HPLC分析方法。方法: 对洛伐他汀原料进行HPLC色谱系统的筛选与优化。用析因设计筛选色谱柱系统。采用中心组合设计,优化梯度洗脱时间、流速和柱温。最优色谱条件为: C₁₈柱(4.6 mm×250 mm,5 μm),以乙腈-0.01%磷酸溶液(65∶35)为流动相,流速1.0 mL·min^-1,梯度洗脱时间为40 min,检测波长为238 nm,柱温为30 ℃。结果: 洛伐他汀色谱保留时间约为10 min,与其有关物质分离良好;最低检测限为0.25 ng。结论: 确立的色谱条件,集目前各国药典测定洛伐他汀有关物质分析方法的优势为一体,测定结果准确,操作方便,可有效地控制药品质量。
 

Objective: Derived from Q_bD(quality by design) and its experimental design, an HPLC method was optimized for the determination of lovastatin. Method: Initially, a full factorial design was used in order to screen chromatographic column system, followed by the optimization of gradient elution time,column temperature and of mobile phase with the aid of central composite design.The separation was achieved by using a reversed phase chromatographic column(C₁₈, 250 mm×4.6 mm, 5 μm) with gradient eluent composed of acetonitrile-0.01% phosphoric acid(65∶ 35) at a wavelength of 238 nm. The gradient elution time was 40 min, column temperature was set at 30 ℃ and flow rate of mobile phase was 1.0 mL·min^-1. Results: The retention time of lovastatin was about 10 minutes. The resolution with its related compounds was good. The limit of detection was 0.25 ng. Conclusion: The developed method highlights the advantages of different analytical methods of lovastatin from pharmacopeias, found to be sensitive ,accurate and convenient, being able to control the drug quality efficiently.