A sensitive, precise, accurate, and specific isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the simultaneous separation and determination of zolmitriptan, naratriptan, dihydroergotamine, ketotifen, and pizotifen in pharmaceutical formulations has been developed and validated. An experimental design was applied for the optimization of the chromatographic parameters. A two-level full factorial 2^k was used for studying the interaction between the variables to be optimized: the percentage of acetonitrile in the mobile phase, mobile-phase pH, nature of the buffer, and column oven temperature. The most significant parameters are the percentage of acetonitrile and the mobile-phase pH. These significant parameters were optimized using the Doehlert matrix. The optimum separation was achieved by means of a Waters XBridge C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of acetonitrile and a 10 mM sodium perchlorate buffer (38 : 62, v/v) at a flow rate of 1.0 mL·min⁻¹ and UV detection at 220 nm. The selectivity, method linearity, accuracy, and precision were examined as part of the method validation. The described method shows excellent linearity over a range of 30 to 70 μg·mL⁻¹ for all compounds with correlation coefficients higher than 0.995. The standard deviations of the intraday and interday precision were between 0.75 and 1.94%. The validated method was successfully applied to perform routine analysis of these compounds in different pharmaceutical products such as syrups and tablets. In the presence of some preservatives, it was found that there were no peaks at the related peak locations.

中文翻译：

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因子和多勒设计在同时分离和测定RP-HPLC-UV药物制剂中偏头痛药物的设计中的应用。

已开发并验证了一种灵敏，精确，准确且特异的等度反相高效液相色谱（RP-HPLC）方法，用于同时分离和测定药物制剂中的佐米曲普坦，那拉曲普坦，二氢麦角胺，酮替芬和吡唑替芬。实验设计用于色谱参数的优化。两级全阶乘2 ^k用于研究要优化的变量之间的相互作用：流动相中乙腈的百分比，流动相pH，缓冲液的性质和柱箱温度。最重要的参数是乙腈的百分比和流动相的pH。使用Doehlert矩阵优化了这些重要参数。最佳分离通过有Waters XBridge C18柱（250毫米×4.6毫米，5来实现 μ（62，V / V 38）在一个流量m），流动相由乙腈和10mM的高氯酸钠缓冲速度1.0 mL·min ^-1和在220 nm处进行紫外线检测。作为方法验证的一部分，检查了选择性，方法线性，准确性和精密度。对于相关系数高于0.995的所有化合物，所描述的方法在30至70μg ·mL ^-1的范围内均显示出极好的线性 。日内和日间精度的标准偏差在0.75和1.94％之间。验证的方法已成功应用于对不同药物产品（如糖浆和片剂）中的这些化合物进行常规分析。在存在一些防腐剂的情况下，发现在相关峰位置没有峰。