Kirkpatrick Douglas, Fain Margaret, Yang Jingyue, Santos Leonel, Anthony Clydewyn
Food and Drug Administration, CDER, Division of Pharmaceutical Analysis, St Louis, MO 63110, 645 S Newstead Avenue, Saint Louis, MO, 63110, United States.
United States Pharmacopeia, Rockville, MD, 20852, United States.
Sep Sci Plus. 2020 Jan;3(1-2):4-11. doi: 10.1002/sscp.201900084.
Many over-the-counter drug products lack official compendial analytical methods. As a result, the United States Pharmacopeia and the United States Food and Drug Administration are seeking to develop and validate new methods to establish analysis standards for the assessment of the pharmaceutical quality of over-the-counter drug products. Diphenhydramine and phenylephrine hydrochloride oral solution, a combination drug product, was identified as needing a compendial standard. Therefore, an ultra-high-performance liquid chromatography method was developed to separate and quantify the two drug compounds and eleven related organic impurities. As part of a robustness study, the separation was demonstrated using different high-performance liquid chromatography systems and columns from different manufacturers, and showed little dependence with changes in flow rate, column temperature, detection wavelength, injection volume and mobile phase gradient. The method was then validated conformant with the International Council for Harmonisation guidelines. For impurities, adequate specificity, linearity, accuracy and precision were demonstrated. For assay, a slight modification to the injection volume was necessary to achieve adequate analytical performance. With successful development and validation, these methods were shown to be suitable for their intended purpose and may be considered for adoption as compendial procedures.
许多非处方药品缺乏官方药典分析方法。因此，美国药典委员会和美国食品药品监督管理局正在寻求开发和验证新方法，以建立用于评估非处方药品药学质量的分析标准。一种复方药品——苯海拉明和盐酸去氧肾上腺素口服溶液，被确定需要一个药典标准。因此，开发了一种超高效液相色谱法来分离和定量两种药物成分以及11种相关有机杂质。作为稳健性研究的一部分，使用不同制造商的不同高效液相色谱系统和色谱柱进行了分离，结果表明该分离对流速、柱温、检测波长、进样体积和流动相梯度的变化依赖性很小。然后按照国际协调理事会指南对该方法进行了验证。对于杂质，证明了其具有足够的专属性、线性、准确度和精密度。对于含量测定，需要对进样体积进行轻微调整以实现足够的分析性能。随着方法的成功开发和验证，这些方法被证明适用于其预期目的，并可考虑作为药典方法采用。
