In view of the US pharmacopeia (USP)-proposed general chapter $$\left\langle {1220} \right\rangle$$ 1220 “The Analytical Procedure Lifecycle” and ICH-proposed ICHQ14 guideline “Analytical Procedure Development”, application of quality by design approach during analytical method development gains a significant importance. Methods developed by QbD approach will be more robust and thereby decrease efforts for method performance verification and post approval changes. Additionally, these methods will be more QC friendly as out of trend or out of specification results due to incompetent methods will be reduced and it will support the approach of life cycle management for analytical procedures. The present study deals with the development of an analytical targeted profile (ATP)-based, rapid, specific, precise, and mass-compatible RP-UPLC method with proven design space (DS) for the quantitative determination of Haloperidol and its degradation products in Haloperidol drug substance and Haloperidol 1 mg tablets. Using 5 different column chemistries, 4 different pH ranges, oven temperatures, and flow rates as variables experiments were carried out and statistically evaluated to finalize the chromatographic conditions. The significance and interaction effects of variables on the critical attributes (tailing factor and resolution) were evaluated through statistical analysis like analysis of variance (ANOVA). DOE study was also applied for the sample preparation to prove robustness of the sample preparation procedure. Forced degradation study was carried to demonstrate the stability-indicating nature of the method. Validation for active and available impurities was performed as per ICH and ANVISA guidelines and the method was found to be linear, accurate, specific, precise, and robust. Specificity of the method was confirmed orthogonally using QDa (mass detector) along with PDA detector. The method can be employed for release and stability testing of Haloperidol drug substance as well as Haloperidol 1 mg tablets.

中文翻译：

---

用于氟哌啶醇原料药和氟哌啶醇 1 mg 片剂中氟哌啶醇含量测定和纯度的统计设计、靶向轮廓 UPLC 方法开发

鉴于美国药典 (USP) 提议的通则 $$\left\langle {1220} \right\rangle$$ 1220“分析程序生命周期”和 ICH 提议的 ICHQ14 指南“分析程序开发”，质量应用在分析方法开发过程中，通过设计方法获得了显着的重要性。通过 QbD 方法开发的方法将更加稳健，从而减少方法性能验证和批准后更改的工作量。此外，这些方法将更加 QC 友好，因为将减少由于不称职的方法导致的不符合趋势或不符合规范的结果，并将支持分析程序的生命周期管理方法。本研究涉及开发基于分析靶向谱 (ATP) 的、快速、特异、精确、和质量兼容的 RP-UPLC 方法，具有经过验证的设计空间 (DS)，用于定量测定氟哌啶醇原料药和氟哌啶醇 1 mg 片剂中的氟哌啶醇及其降解产物。使用 5 种不同的色谱柱化学成分、4 种不同的 pH 值范围、柱箱温度和流速作为变量进行实验并进行统计评估以最终确定色谱条件。通过方差分析 (ANOVA) 等统计分析评估变量对关键属性（拖尾因子和分辨率）的显着性和交互作用。DOE 研究也用于样品制备，以证明样品制备程序的稳健性。进行了强制降解研究以证明该方法的稳定性指示性质。根据 ICH 和 ANVISA 指南对活性杂质和可用杂质进行验证，发现该方法具有线性、准确、特异性、精确性和稳健性。使用 QDa（质量检测器）和 PDA 检测器正交确认了该方法的特异性。该方法可用于氟哌啶醇原料药和氟哌啶醇1mg片剂的释放和稳定性试验。