Quality of realgar and its influencing factors based on toxicity

JIANG La1,2 XU Huan-hua2,3 JIANG Zhen-hong4 YANG Shi-han2 SHI Qiao-li5 MA Zeng-chun2,3 GAO Yue1,2 CHEN Zhi-wu1

(1.Department of Pharmacology, Anhui Medical University, Hefei, China 230032)
(2.Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, China 100850)
(3.Guangdong Pharmaceutical University, Guangzhou, China 510006)
(4.Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China 330006)
(5.State Key Laboratory of Drug Metabolism, Hematological Pharmacology Research Room, Institute of Transfusion Medicine, Beijing, China 100850)

【Abstract】The results of a toxicity analysis showed differences from those of the existing experimental data. Therefore, HPLC-ICP-MS was used to analyze the soluble arsenic content at different valences in realgar prepared with water grind processing, which were collected from three companies. The results showed that the free arsenic of the three companies did not exceed the limit of Chinese Pharmacopoeia. However, if the free arsenic was calculated based on the total value of As (Ⅲ) + As (Ⅴ), free arsenic of one company exceeded the limit of Chinese Pharmacopoeia. The method of determining free arsenic in Chinese Pharmacopoeia was ancient Cai’s arsenic detection method, which had a certain limitation and failed to effectively avoid the toxicity of remaining arsenics except for trivalent arsenic. Then, we examined the effects of water and temperature on the content and form of soluble arsenic in realgar. The results showed that the content of soluble arsenic increased with the rise of water content, and the form of soluble arsenic did not change, there were only As (Ⅲ) and As (Ⅴ); With the simple temperature factor, there was an increasing trend in the content of soluble arsenic in the samples, the maximum increment was As (Ⅲ) 2.489 mg·g−1and As (Ⅴ) 0.546 mg·g−1; When water and temperature played an synergistic effect, the increase of soluble arsenic in the samples significantly changed, the maximum increment was As (Ⅲ) 23.690 mg·g−1, As (Ⅴ) 0.468 mg·g−1, respectively. Through comprehensive analysis, we believed that the quality of realgar was susceptible to water content and temperature. Both of the single effect of water content and the synergistic effect of water and temperature can significantly change the content of soluble arsenic in realgar, and the water content was a high-risk factor. In the current Chinese Pharmacopoeia of 2015 edition, the free arsenic detection method had limitations, hence new techniques shall be introduced; At the same time, realgar does not have a water content inspection item in the current pharmacopoeia, which shall be added. However, due to the limit of water content, more in-depth studies are required.

【Keywords】 realgar; water content; temperature; soluble arsenic; quality control;


【Funds】 National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2015ZX09501004-003-003)

Download this article

(Translated by XIONG Y)


    [1] Liang AH, Li CY, Wang JH, et al. Toxicity study of realgar [J].China Journal of Chinese Materia Medica, 2011, 36 (12): 1889 (in Chinese).

    [2] Chinese Pharmacopoeia. Vol. I [S]. 2015: 336 (in Chinese).

    [3] Zhang YW, Ma XJ, Yang CM. 含朱砂、雄黄的中药制剂的质量控制及安全性评价问题分析 [J]. China Journal of Chinese Materia Medica, 2010, 35 (11):1501 (in Chinese).

    [4] Li SS, Lin QH, Xu HF, et al. Quality Investigation of Realgar in Commercially Available Medicinal Materials and Decoction Pieces [J]. Acta Chinese Medicine and Pharmacology, 2016, 44 (2): 10 (in Chinese).

    [5] Pei YM, Yang SY, Gu JH. 牛黄解毒颗粒剂制备工艺中雄黄的炮制方法及其可溶性砷盐的含量测定 [J]. China Journal of Chinese Materia Medica, 1995, 20 (10): 599 (in Chinese).

    [6] Li CF. 雄黄及含雄黄中成药的质量控制研究 [D]. Beijing: Beijing University of Chinese Medicine, 2017 (in Chinese).

    [7] Li H, Zhao MH, Liang AH, et al. Comparative Study on Contents of As2S2 and As2O3 in Realgar and Processed Products [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2013, 19 (2): 49 (in Chinese).

    [8] Zhang YJ, Qiang SP, Song M, et al. Arsenic speciation in rat plasma after oral administration of realgar and Niu Huang Jie Du Pian [J]. Acta Pharmaceutica Sinica, 2016, 51 (7): 1130 (in Chinese).

    [9] Chen SZ, Du ZX, Liu LP, et al. Analysis of Arsenic Metabolites of Realgar in Rat Viscera by HPLC-ICP-MS [J]. Chinese Journal of Analytical Chemistry, 2014, 42 (3): 349 (in Chinese).

    [10] Chen, SZ, Liu LP, Du ZX, et al. The presence form and analytic technology of arsenic in food [J]. Chinese Journal of Food Hygiene, 2014, 26 (3): 296 (in Chinese).

    [11] Ye ZG, Zhang GP. Progress of Safety Evaluation of Traditional Chinese Medicines and Its Strategy in Further Studies [J]. Progress of Safety Evaluation of Traditional Chinese Medicines and Its Strategy in Further Studies, 2014, 20 (16): 1 (in Chinese).

    [12] Jia W, Jiang J, Liu P, et al. Application of metabonomics in complicated theory system research of traditional Chinese medicine [J].China Journal of Chinese Materia Medica, 2006, 31 (8): 621 (in Chinese).

    [13] Griffin. Blood’s 70th anniversary: arsenic—from poison pill to magic bullet [J]. Blood, 2016, 127 (14): 1729.

This Article


CN: 11-2272/R

Vol 42, No. 24, Pages 4782-4787

December 2017


Article Outline


  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion and suggestions
  • References