Optimization of a spectrofluorimetric method based on a central composite design for the determination of potassium losartan in pharmaceutical products

Here, a spectrofluorimetric method for the determination of potassium losartan (PL) in pharmaceutical products is described. The effects of critical parameters, pH, acid molarity, and temperature, on the fluorescence intensity of PL were analyzed, and these parameters were optimized using a central composite design (CCD). The highest fluorescent intensity at excitation (λex) and emission (λem) wavelengths of 248 nm and 410 nm, respectively, was achieved using 0.01 M sulfurous acid (pH 2) at 21.6 °C. Under optimum conditions, the method was linear from 0.025-0.5 µg/mL, with a reasonably high correlation coefficient (0.9993). Furthermore, the method was very sensitive (LOQ, 0.006), accurate (RE, ≤7.06), and precise (%RSD, ≤6.51). After development and validation of the method, samples containing PL were analyzed with this method, and the obtained data were statistically compared with those obtained with a previously published reference method using a two one-sided equivalence test (TOST). According to the data, the results from the proposed and reference assays were equivalent.本文报道了一种用于测定药物制剂中氯沙坦钾（potassium losartan，PL）的荧光分光光度法（spectrofluorimetric method）。研究分析了pH、酸摩尔浓度及温度等关键参数对PL荧光强度的影响，并采用中心复合设计（central composite design，CCD）对上述参数进行了优化。在21.6 ℃、以0.01 M亚硫酸（sulfurous acid，pH=2）为介质的条件下，PL在激发波长（λex）248 nm、发射波长（λem）410 nm处获得了最高荧光强度。在最优实验条件下，该方法的线性范围为0.025~0.5 µg/mL，相关系数达0.9993。此外，该方法灵敏度优异，定量限（limit of quantitation，LOQ）为0.006 µg/mL，准确度良好（相对误差（relative error，RE）≤7.06%），精密度可靠（相对标准偏差（relative standard deviation，%RSD）≤6.51%）。在该方法开发并完成验证后，采用其对含PL的样品进行检测，并将所得数据与已发表的参考方法通过双向单侧等效检验（two one-sided equivalence test，TOST）进行统计学对比。结果显示，本方法与参考方法的检测结果具有等效性。