Abstract Analytical techniques with sound scientific understanding and assured regulatory flexibilities for post-approval change management are the need of the current pharma scenario. In the present study, the recent concept of analytical procedure development is utilized along with quality management concepts to address the above issue. A new chromatographic method was developed for quantifying a novel antipsychotic agent pimavanserin tartarate in its dosage form. Critical method variables were identified and were investigated for their possible effect on critical analytical attributes viz. analyte retention, plate count and peak tailing. Methanol%, flow rate, and pH of mobile phase were the sorted critical method variables and were optimized using systematic Box-Behnken experimentation. The optimized chromatography used C18 column (150 × 4.6 mm, 5 µm) and methanol: phosphate buffer (pH 3.5) (80:20, v/v) as the mobile phase with a flow of 1 mL/min. Pimavanserin was separated from tartaric acid (resolution >7.5). Diode array detection at 226 nm presented accurate and precise quantification of pimavanserin. Linear responses were obtained over 0.5–100 µg/mL of pimavanserin. Further, the procedure performance capability index was measured by using Monte-Carlo simulation. In a nutshell, the present studies reveal the aptness of hyphenating chemometry with this novel concept for robust quantification of pimavanserin. Graphical Abstract

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分析程序开发：基于化学计量学的超快 LC 估计药物中匹马万色林的应用概念

摘要 具有良好科学理解和确保批准后变更管理的监管灵活性的分析技术是当前制药方案的需要。在本研究中，分析程序开发的最新概念与质量管理概念一起用于解决上述问题。开发了一种新的色谱方法，用于对剂型中的新型抗精神病药物匹马万色林酒石酸盐进行定量。确定了关键方法变量并研究了它们对关键分析属性的可能影响，即。分析物保留、塔板数和峰拖尾。流动相的甲醇百分比、流速和 pH 值是排序的关键方法变量，并使用系统的 Box-Behnken 实验进行了优化。优化的色谱使用 C18 柱（150 × 4.6 mm，5 µm) 和甲醇：磷酸盐缓冲液 (pH 3.5) (80:20, v/v) 作为流动相，流速为 1 mL/min。Pimavanserin 与酒石酸分离（分辨率 >7.5）。226 nm 的二极管阵列检测提供了匹马万色林的准确定量。在 0.5–100 µg/mL 匹马万色林中获得线性响应。此外，使用蒙特卡罗模拟测量程序性能能力指数。简而言之，目前的研究揭示了将化学计量学与这种新概念结合起来对 pimavanserin 进行稳健量化的适用性。图形概要 226 nm 的二极管阵列检测提供了匹马万色林的准确定量。在 0.5–100 µg/mL 匹马万色林中获得线性响应。此外，使用蒙特卡罗模拟测量程序性能能力指数。简而言之，目前的研究揭示了将化学计量学与这种新概念结合起来对 pimavanserin 进行稳健量化的适用性。图形概要 226 nm 的二极管阵列检测提供了匹马万色林的准确定量。在 0.5–100 µg/mL 匹马万色林中获得线性响应。此外，使用蒙特卡罗模拟测量程序性能能力指数。简而言之，目前的研究揭示了将化学计量学与这种新概念结合起来对 pimavanserin 进行稳健量化的适用性。图形概要