Objective: To establish an ICP-MS method to detect the residual amounts of Class 1 elemental impurities [arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb)], and Class 2A elemental impurities [cobalt (Co), nickel (Ni), and vanadium (V)] in mannitol according to ICH Q3D(R2). Methods: ICP-MS method was adopted, with helium as the carrier gas. HMI-8 plasma mode was selected, with a sampling depth of 10.0 mm, radio frequency power of 1 600 W, carrier gas flow rate of 0.8 L·min-1, atomization gas flow rate of 0.8 L·min-1, auxiliary gas flow rate of 0.8 L·min-1, plasma gas flow rate of 15.0 r·min-1, peristaltic pump speed of 0.10 r·min-1, and atomization chamber temperature of 2.0 ℃. The analysis method is the internal standard method. Results: The linear correlation coefficient r of 7 elemental impurities was greater than 0.999. The recovery rates were within the range of 90.0%-110.0%. The RSD of recovery rate was less than 5.0%. The RSD of precision rate was less than 7.0%. The contents of 7 elemental impurities in 73 batches of samples were all less than permitted daily exposure(PDE) for injection set by ICH Q3D(R2). Conclusion: This method is highly sensible, reproducible, accurate and can precisely determine the Class 1 and Class 2A element impurities in mannitol; The residual risk of impurities in Class 1 and Class 2A elements in commercially available mannitol is low.
GUO Ya-juan, WANG Cai-mei, HU Shu-jun, CHEN Ying
. Determination of elemental impurities in mannitol by ICP-MS[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(5)
: 804
-810
.
DOI: 10.16155/j.0254-1793.2023.05.10
[1] 张宏康,王中瑗,许佳璇,等.食品中重金属检测方法研究进展[J].食品安全质量检测学报,2016,7(5): 1844
ZHANG HK,WANG ZY,XU JX. Progress in studies of heavy mentals in food[J].J Food Saf Qual Assess, 2016, 7(5): 1844
[2] ICH. 元素杂质指导原则Q3D(R2)[S]. 2022
ICH. Coordination Guidelines Elemental Impurities Guideline Q3D(R2)[S]. 2022
[3] 詹天荣,宋金明.甘露醇的药用研究进展[J].中国海洋药物杂志,2003,22(3):57
ZHAN TY,SONG JM. Progress in studies of mannitol in medicinal application[J].Chin J Mar Drugs, 2003, 22(3):57
[4] 魏倩倩.甘露醇的生产与应用研究进展[J].食品工业科技,2010,12(31):401
WEI QQ. Research progress in preparation and application of mannitol[J].Sci Technol Food Ind, 2010, 12(31):401
[5] 王春霞,王晓梅,张娟娟,等.甘露醇的生产应用进展[J].轻工科技,2013,29(8):43
WANG CX,WANG XM,ZHANG JJ. Progress of mannitol in production and application[J].Light Ind Sci Technol, 2013,29(8):43
[6] FRANCIS D. Process for The Manufacture of Mannito l:US,5466795[P].1995
[7] 中华人民共和国药典2020年版.二部[S].2020:140
ChP 2020.Vol Ⅱ[S].2020:140
[8] 徐昕怡,洪小栩. 从ICH Q3D元素杂质指导原则欧美药典实施历程探索《中国药典》转化路径[J].中国食品药品监管,2020,10(2):22
XU XY, HONG XX. The discussion of implementation of ICH Q3D element impurities guideline in Chinese Pharmacopoeia based on the EP & USP implementation process[J].China Food Drug Admin Mag, 2020,10(2):22
[9] USP 43-NF 38[S].2020: 150
[10] EP 10.0[S].2020: 144
[11] JP 17[S].2016: 2893
[12] 朱莉,赵瑜,姚尚辰,等.药物中元素杂质检测技术研究最新进展[J].分析测试学报,2020,39(4):547
ZHU L, ZHAO Y, YAO SC. Research progress on detection techniques for elemental impurities in drugs[J].J Instrum Anal,2020, 39(4):547
[13] 李耀磊,金红宇,韩笑.电感耦合等离子体质谱测定法中汞元素记忆效应与稳定性研究[J].中国药学杂志,2019:54(1):53
LI YL, JING HY, HAN X. Determination of the memory effect and stability of mercury by ICP-MS[J].Chin Pharm J,2019:54(1):53
[14] 朱弘,吴春祥,马生柏.水中微量汞的稳定剂的研究[J].环境研究与监测,2006,19(1): 51
ZHU H,WU CX,MA SB. Study of the stability of mercury in water[J].Environ Res Monit, 2006, 19(1): 51
