Objective: To establish an inductively coupled plasma mass spectrometry (ICP-MS) method for the determination of 25 types of element impurities with potential risks in calcium citrate malate, include Cd, Pb, As, Hg, Co, V, Ni, Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag, Pt, Sb, Li, Ba, Mo, Cu, Sn, Cr and Al. Methods: About 25 mg of sample was taken and placed in a 25 mL bottle (PP), and 1 mL nitric acid and 0.25 mL hydrochloric acid solution were added. The solutions were shake slightly to dissolve, and diluted with ultra-pure water. Agilent 7900 ICP-MS combined with automatic sampler was used for sample determination in He mode. Concentric atomizer was used, atomizing gas flow rate was 1.05 L·min-1, atomizing chamber temperature was 2 ℃, sample lifting speed was 0.1 r·s-1, RF power was 1 550 W, sampling depth was 10 mm, and sample flow rate was 1.05 L·min-1. The helium flow rate was 5 mL·min-1, the energy discrimination was 5.0 V, and the elemental impurities in the samples were quantitatively analyzed by standard curve method with internal standard correction. The characteristic isotope (mass number) of each element was selected based on the isotope ratio of each element impurity, and the method was verified by reference to USP 41<233>. Results: The lower detection limits of the 25 impurity elements were 0.002-6.97 μg·L-1, the spiked recoveries were between 70%-150%, and the repeatabilities were no more than 20%, with good precision. According to ICH Q3D method 1 General allowable concentration limit method, 24 elemental impurities in multiple batches of raw materials and preparation samples all met the limit requirements, while some elements exceeded the control threshold (30%PDE), and the risk of aluminum in the samples was low. Considering the uncertainty of the source of raw materials, from the perspective of ensuring product safety, methods should be established to control the quality of raw materials and preparations. Conclusion: Isotope ratio method is an effective method to study the specificity of ICP-MS method. The established method has strong specificity, high accuracy, simple and feasible, and can provide a reference for the verification of elemental impurities in calcium citrate malate and other complex substrates. The method established in this study is able to satisfy the quality control of calcium citrate malate.
JING Yi-wen, ZHANG Qiao, YANG Xiu-yun, WANG Wei, ZHANG Wei-feng, ZHU Li, XIAO Chao-qiang
. Determination of 25 elemental impurities in calcium citrate malate*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(7)
: 1229
-1237
.
DOI: 10.16155/j.0254-1793.2023.07.17
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