Moradiya Mehul R, Solanki Kamlesh P, Shah Purvi A, Patel Kalpana G, Thakkar Vaishali T, Gandhi Tejal R
Anand Pharmacy College, Anand, Gujarat, India.
PDA J Pharm Sci Technol. 2013 Mar-Apr;67(2):164-71. doi: 10.5731/pdajpst.2013.00911.
Carefully designed cleaning validation and its evaluation can ensure that residues of active pharmaceutical ingredient will not carry over and cross-contaminate the subsequent product. UV spectrophotometric and total organic carbon-solid sample module (TOC-SSM) method was developed and validated for the verification and determination of atorvastatin residues in the production area and to confirm the efficiency of the cleaning procedure as per ICH guideline. Atorvastatin was selected on the basis of a worst-case rating approach. It exhibited good linearity in the range of 5 to 25 μg/mL for UV spectrophotometric and 7300 to 83800 μg for the TOC-SSM method. The limit of detection was 0.419 μg/mL and 4.19 μg in the UV spectrophotometric and TOC-SSM methods, respectively. The limit of quantitation was 1.267 μg/mL and 12.69 μg in UV spectrophotometric and TOC-SSM methods, respectively. Percentage recovery from spiked stainless steel plates was found to be 95.37% and 92.82% in UV spectrophotometric and TOC-SSM methods, respectively. The calculated limit of acceptance per swab for atorvastatin (35.65 μg/swab) was not exceeded during three consecutive batches of production after cleaning procedure. Both proposed methods are suitable for quantitative determination of atorvastatin on manufacturing equipment surfaces well below the limit of contamination. The ease of sample preparation permits fast and efficient application of the proposed methods in quantitation of atorvastatin residue with precision and accuracy. Above all, the methodology is of low cost, and is a simple and less time-consuming alternative to confirm the efficiency of the cleaning procedure in pharmaceutical industries.
Carefully designed cleaning validation and its evaluation can ensure that residues of active pharmaceutical ingredient will not carry over and cross-contaminate the subsequent product. Atorvastatin was identified as a potential candidate among existing drug substances in production areas based on a worst-case rating approach. Atorvastatin residues were detected and quantified below acceptance limits after cleaning of production equipment using two proposed methods, namely, the UV spectrophotometric and total organic carbon-solid sample module (TOC-SSM) methods. The ease of sample preparation permits fast and efficient application of the proposed methods in quantitation of atorvastatin residue in production equipment area to confirm the efficiency of the cleaning procedure in pharmaceutical industries. Above all, the methodology is of low cost, and is a simple and less time-consuming alternative for cleaning validation.
精心设计的清洁验证及其评估可确保活性药物成分的残留不会带入并交叉污染后续产品。开发并验证了紫外分光光度法和总有机碳 - 固体样品模块（TOC - SSM）方法，用于生产区域中阿托伐他汀残留的验证和测定，并根据国际人用药品注册技术协调会（ICH）指南确认清洁程序的有效性。基于最坏情况评级方法选择了阿托伐他汀。在紫外分光光度法中，其在5至25μg/mL范围内呈现良好的线性，在TOC - SSM方法中，线性范围为7300至83800μg。紫外分光光度法和TOC - SSM方法的检测限分别为0.419μg/mL和4.19μg。紫外分光光度法和TOC - SSM方法的定量限分别为1.267μg/mL和12.69μg。在紫外分光光度法和TOC - SSM方法中，加标不锈钢板的回收率分别为95.37%和92.82%。在清洁程序后的连续三批生产中，每擦拭取样点阿托伐他汀的计算合格限（35.65μg/擦拭取样点）均未被超过。两种提议的方法均适用于定量测定制造设备表面阿托伐他汀的残留，且残留量远低于污染限度。样品制备简便，使得提议的方法能够快速有效地应用于阿托伐他汀残留量的定量测定，具有精密度和准确度。最重要的是，该方法成本低，是一种简单且耗时较少的替代方法，可用于确认制药行业清洁程序的有效性。
精心设计的清洁验证及其评估可确保活性药物成分的残留不会带入并交叉污染后续产品。基于最坏情况评级方法，阿托伐他汀被确定为生产区域现有原料药中的潜在候选物质。使用两种提议的方法，即紫外分光光度法和总有机碳 - 固体样品模块（TOC - SSM）方法，在清洁生产设备后，检测并定量了阿托伐他汀残留量，其低于合格限度。样品制备简便，使得提议的方法能够快速有效地应用于生产设备区域阿托伐他汀残留量的定量测定，以确认制药行业清洁程序的有效性。最重要的是，该方法成本低，是一种简单且耗时较少的清洁验证替代方法。
