Jenke Dennis, Rivera Christine, Mortensen Tammy, Amin Parul, Chacko Molly, Tran Thang, Chum James
Baxter Healthcare Corporation, Technology Resources Organization, Round Lake, IL 60073 USA.
PDA J Pharm Sci Technol. 2013 Jul-Aug;67(4):354-75. doi: 10.5731/pdajpst.2013.00927.
Nearly 100 individual test articles, representative of materials used in pharmaceutical applications such as packaging and devices, were extracted under exaggerated conditions and the levels of 32 metals and trace elements (Ag, Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ge, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Sb, Se, Si, Sn, Sr, Ti, V, Zn, and Zr) were measured in the extracts. The extracting solvents included aqueous mixtures at low and high pH and an organic solvent mixture (40/60 ethanol water). The sealed vessel extractions were performed by placing an appropriate portion of the test articles and an appropriate volume of extracting solution in inert extraction vessels and exposing the extraction units (and associated extraction blanks) to defined conditions of temperature and duration. The levels of extracted target elements were measured by inductively coupled plasma atomic emission spectroscopy. The overall reporting threshold for most of the targeted elements was 0.05 μg/mL, which corresponds to 0.5 μg/g for the most commonly utilized extraction stoichiometry (1 g of material per 10 mL of extracting solvent). The targeted elements could be classified into four major groups depending on the frequency with which they were present in the over 250 extractions reported in this study. Thirteen elements (Ag, As, Be, Cd, Co, Ge, Li, Mo, Ni, Sn, Ti, V, and Zr) were not extracted in reportable quantities from any of the test articles under any of the extraction conditions. Eight additional elements (Bi, Cr, Cu, Mn, Pb, Sb, Se, and Sr) were rarely extracted from the test articles at reportable levels, and three other elements (Ba, Fe, and P) were infrequently extracted from the test articles at reportable levels. The remaining eight elements (Al, B, Ca, Mg, Na, S, Si, and Zn) were more frequently present in the extracts in reportable quantities. These general trends in accumulation behavior were compared to compiled lists of elements of concern as impurities in pharmaceutical products.
Nearly 100 individual test articles, representative of materials used in pharmaceutical applications such as packaging and devices, were extracted under exaggerated conditions, and the levels of thirty-two metals and trace elements (Ag, Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ge, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Sb, Se, Si, Sn, Sr, Ti, V, Zn, and Zr) were measured in the extracts. The targeted elements could be classified into four major groups depending on the frequency with which they were present in the extractions reported in this study: those elements that were not extracted in reportable quantities from any of the test articles under any of the extraction conditions, those elements that were rarely extracted from the test articles at reportable levels, those elements that were infrequently extracted from the test articles at reportable levels, and those elements that were more frequently present in the extracts in reportable quantities.
在极端条件下提取了近100种代表制药应用（如包装和器械）中使用材料的单个测试物品，并测量了提取物中32种金属和微量元素（银、铝、砷、硼、钡、铍、铋、钙、镉、钴、铬、铜、铁、锗、锂、镁、锰、钼、钠、镍、磷、铅、硫、锑、硒、硅、锡、锶、钛、钒、锌和锆）的含量。提取溶剂包括低pH和高pH的水性混合物以及有机溶剂混合物（40/60乙醇水）。通过将适量的测试物品和适量体积的提取溶液放入惰性提取容器中，并将提取单元（以及相关的提取空白）暴露于规定的温度和持续时间条件下进行密封容器提取。通过电感耦合等离子体原子发射光谱法测量提取的目标元素含量。大多数目标元素的总体报告阈值为0.05μg/mL，这对应于最常用提取化学计量（每10mL提取溶剂1g材料）下的0.5μg/g。根据在本研究报告的250多次提取中出现的频率，目标元素可分为四大类。在任何提取条件下，13种元素（银、砷、铍、镉、钴、锗、锂、钼、镍、锡、钛、钒和锆）从任何测试物品中均未提取出可报告量。另外8种元素（铋、铬、铜、锰、铅、锑、硒和锶）很少从测试物品中提取出可报告水平的量，另外3种元素（钡、铁和磷）很少从测试物品中提取出可报告水平的量。其余8种元素（铝、硼、钙、镁、钠、硫、硅和锌）更频繁地以可报告量出现在提取物中。将这些积累行为的一般趋势与作为药品杂质的关注元素汇编列表进行了比较。
在极端条件下提取了近100种代表制药应用（如包装和器械）中使用材料的单个测试物品，并测量了提取物中32种金属和微量元素（银、铝、砷、硼、钡、铍、铋、钙、镉、钴、铬、铜、铁、锗、锂、镁、锰、钼、钠、镍、磷、铅、硫、锑、硒、硅、锡、锶、钛、钒、锌和锆）的含量。根据在本研究报告的提取中出现的频率，目标元素可分为四大类：在任何提取条件下从任何测试物品中均未提取出可报告量的元素、很少从测试物品中提取出可报告水平的元素、很少从测试物品中提取出可报告水平的元素以及更频繁地以可报告量出现在提取物中的元素。
