Si-Qi Zhu, Ji-Wu Liu*, Xiao Gu, Jin-Qi Zheng* and Pei-Xi Zhu Pages 82 - 87 ( 6 )
Background: Aluminum (Al) is classified as other elements by ICH, and its permitted daily exposure (PDE) has not been established. As it might cause compromised renal function, guidelines, regional regulations and practices need to be addressed. According to the United States Pharmacopeia 41 and the Japanese Pharmacopoeia 17, the aluminum content of large-volume parenterals (LVPs) used in total parenteral nutrition (TPN) therapy must not exceed 25 ng mL-1. Therefore, the package insert of LVPs used in TPN therapy must state the content of aluminum.
Objective: A new microwave assisted acid digestion pretreatment together with inductively coupled plasma mass spectrometry (ICP-MS) method was developed for the determination of aluminum content in Dextran 40 Glucose Injection. The method was successfully applied for quality evaluation of commercial Dextran 40 Glucose Injection.
Methods: Samples were digested by a mixture of nitric acid and hydrochloric acid, with the assistance of microwave. After that, ICP-MS in KED mode was employed to analyze the samples.
Results: The method showed a good linearity (r2=0.9999) within the range of 2~100 ng mL-1, with the limit of detection and quantitation of 0.482 ng mL-1 and 1.61 ng mL-1, respectively. A good precision was obtained with relative standard deviation (RSD) of 8.8% (n=6). The spike recoveries with low, middle and high Al content in 9 sample were 102.2%~107.4%.
Conclusion: The developed method was successfully applied for the analysis of Al content in 44 batches of Dextran 40 Glucose Injection produced by 9 pharmaceutical companies from domestic or international enterprises. The Al content of Dextran 40 Glucose Injection varied greatly between different enterprises or different batches. Meanwhile, among total of 44 batches, the Al content in 3 batches of Dextran 40 Glucose Injection exceeded the limitation of 25 ng mL-1, which might cause potential safety problems.
Aluminum, Dextran 40 Glucose Injection, ICP-MS, elemental impurity, microwave digestion, USP<233>.
National Anti-Drug Laboratory Zhejiang Regional Center (Zhejiang Anti-Drug Technology Center), Hangzhou, Zhejiang, National Anti-Drug Laboratory Zhejiang Regional Center (Zhejiang Anti-Drug Technology Center), Hangzhou, Zhejiang, Zhejiang Institute for Food and Drug Control (Key Laboratory of Core Technology for Generic Drug Evaluation, China Drug Administration), Hangzhou, Zhejiang, Zhejiang Institute for Food and Drug Control (Key Laboratory of Core Technology for Generic Drug Evaluation, China Drug Administration), Hangzhou, Zhejiang, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang