Haidar Ahmad Imad A, Tam James, Li Xue, Duffield William, Tarara Thomas, Blasko Andrei
Novartis Pharmaceuticals Corporation, San Carlos, CA, USA.
Novartis Pharmaceuticals Corporation, San Carlos, CA, USA.
J Pharm Biomed Anal. 2017 Feb 5;134:108-115. doi: 10.1016/j.jpba.2016.11.022. Epub 2016 Nov 18.
The parameters affecting the recovery of pharmaceutical residues from the surface of stainless steel coupons for quantitative cleaning verification method development have been studied, including active pharmaceutical ingredient (API) level, spiking procedure, API/excipient ratio, analyst-to-analyst variability, inter-day variability, and cleaning procedure of the coupons. The lack of a well-defined procedure that consistently cleaned coupon surface was identified as the major contributor to low and variable recoveries. Assessment of acid, base, and oxidant washes, as well as the order of treatment, showed that a base-water-acid-water-oxidizer-water wash procedure resulted in consistent, accurate spiked recovery (>90%) and reproducible results (S≤4%). By applying this cleaning procedure to the previously used coupons that failed the cleaning acceptance criteria, multiple analysts were able to obtain consistent recoveries from day-to-day for different APIs, and API/excipient ratios at various spike levels. We successfully applied our approach for cleaning verification of small molecules (MW<1000Da) as well as large biomolecules (MW up to 50,000Da). Method robustness was greatly influenced by the sample preparation procedure, especially for analyses using total organic carbon (TOC) determination.
为开发定量清洁验证方法，研究了影响从不锈钢试片表面回收药物残留的参数，包括活性药物成分（API）水平、加样程序、API/辅料比例、分析人员间的差异、日间差异以及试片的清洁程序。缺乏始终能清洁试片表面的明确程序被确定为回收率低且变化不定的主要原因。对酸、碱和氧化剂洗涤以及处理顺序的评估表明，碱 - 水 - 酸 - 水 - 氧化剂 - 水的洗涤程序可实现一致、准确的加样回收率（>90%）和可重现的结果（S≤4%）。通过将此清洁程序应用于先前未通过清洁验收标准的用过的试片，多名分析人员能够在不同日期针对不同的API以及不同加样水平的API/辅料比例获得一致的回收率。我们成功地将我们的方法应用于小分子（MW<1000Da）以及大分子生物分子（MW高达50,000Da）的清洁验证。方法稳健性受样品制备程序的影响很大，尤其是对于使用总有机碳（TOC）测定的分析。
