目的:采用氢化物发生-原子荧光光谱法(HG-AFS)测定7种安宫牛黄丸中的总砷、总汞、可溶性砷及可溶性汞含量,分析比较不同样本间的差异,为含朱砂、雄黄等中药复方制剂质量安全评价提供参考。方法:采用湿法消解提取样品中的总砷和总汞,同时模拟人体胃肠道环境,通过人工胃液及人工肠液仿生提取可溶性砷及可溶性汞,结合HG-AFS方法分别测定砷、汞总量及溶出量。砷检测波长为193.7 nm,灯电流60 mA,负高压250 V;汞检测波长为253.7 nm,灯电流30 mA,负高压280 V。结果:总砷、汞及可溶性砷、汞的线性相关系数均大于0.999;精密度、回收率、重复性、稳定性良好,总砷和可溶性砷的RSD均小于5%,总汞和可溶性汞的RSD均小于10%。安宫牛黄丸中总砷、总汞、可溶性砷及可溶性汞的含量分别为39.07～44.87 mg·g-1、15.05～39.92 mg·g-1、0.418 9～1.335 mg·g-1、5.04～8.46 μg·g-1。结论:各品种安宫牛黄丸总汞及可溶性砷含量差异显著,提示可能存在安全性风险,建议《中华人民共和国药典》增加与砷、汞相关项目的检测与控制。
Objective: To develop an hydride generation-atomic fluorescence spectrometry(HG-AFS) method for the determination of total arsenic, total mercury, soluble arsenic and soluble mercury, and compare the diffe-rences in 7 kinds of Angong Niuhuang pills in order to provide references for the quality and safety evaluation of cinnabar and realgar containing traditional Chinese medicine compound preparations. Methods: Total and dissolution amount of arsenic and mercury were determined by HG-AFS after wet digestion and artificial gastric or intestinal juice extraction, respectively. The detection wavelength of arsenic was 193.7 nm, and the lamp current and negative pressure were 60 mA and 250 V, respectively. The detection wavelength of mercury was 253.7 nm, and the lamp current and negative pressure were 30 mA and 280 V, respectively. Results: The linear correlation coefficients of total arsenic, total mercury, soluble arsenic and soluble mercury were all above 0.999. The results of precision, recovery, repeatability and stability test of arsenic and mercury were all good with RSDs below 5% and 10%, respectively. The contents of total arsenic, total mercury, soluble arsenic and soluble mercury in Angong Niuhuang pills were 39.07-44.87 mg·g-1, 15.05-39.92 mg·g-1, 0.418 9-1.335 mg·g-1 and 5.04-8.46 μg·g-1, respectively. Conclusion: The contents of total mercury and soluble arsenic in Angong Niuhuang pills are significantly varied, which may cause potential safe risks. Therefore, test items of arsenic and mercury should be included in Chinese Pharmacopoeia.
[1] 郑芳昆, 龙登毅, 贝筝, 等. 安宫牛黄丸联合常规治疗对急性脑梗死恢复期患者的临床疗效[J].中成药, 2021, 43(2): 381
ZHENG FK, LONG DY, BEI Z, et al. Clinical effect of Angong Niuhuang pills combined with conventional treatment on patients with acute cerebral infarction in recovery period[J].Chin Tradit Pat Med, 2021, 43(2): 381
[2] LV L, ZHENG J, ZHANG Y, et al. Respiratory nursing care with Angong Niuhuang pills for patients with chronic obstructive pulmonary disease following cardiac surgery[J].Jpn J Nurs Sci, 2020, 18(1): e12344
[3] 刘芬芬, 周亚博,路永坤, 等. 安宫牛黄丸辅助治疗脑出血有效性与安全性的系统评价[J].中国中药杂志, 2021. https://doi.org/10.19540/j.cnki.cjcmm.20210316.501.
LIU FF, ZHOU YB, LU YK, et al. Systemic evaluation of the efficacy and safety of Angong Niuhuang pills in adjuvant treatment of cerebral hemorrhage[J].China J Chin Mater Med, 2021. https://doi.org/10.19540/j.cnki.cjcmm.20210316.501
[4] 贡庆欣, 李文君, 张进. 原子吸收分光光度法测定安宫牛黄丸中雄黄和朱砂的含量[J].中国卫生标准管理, 2018, 9(21): 89
GONG QX, LI WJ, ZHANG J. Determination of realgar and cinnabar in Angong Niuhuang pills by atomic absorption spectrophotometry[J].China Health Stand Manage, 2018, 9(21): 89
[5] LU YT, YANG DY, SONG XN, et al. Bioaccessibility and health risk assessment of mercury in cinnabar containing traditional Chinese medicines[J].J Trace Elem Med Biol, 2017, 44: 17
[6] WU X, GUAN R, LIU YX, et al. Comparative health risk assessment of realgar and NiuHuangJieDu tablets based on tissue arsenic levels after multiple oral administration to rats[J].J Ethnopharmacol, 2020, 249: 112370
[7] WU X, WU SH, LIU YX, et al. Health risk assessment of arsenic in realgar and NiuHuangJieDu tablets based on pharmacokinetic study[J].J Trace Elem Med Biol, 2018, 48: 81
[8] 王辰洋, 金鹏飞, 邝咏梅, 等. ICP-MS研究含雄黄中成药中的砷元素在胃肠液中的溶出特性[J].沈阳药科大学学报, 2015, 32(11): 853
WANG CY, JIN PF, KUANG YM, et al. Dissolution characteristics of arsenic in gastrointestinal fluids for realgar-containing traditional Chinese medicines by ICP-MS[J].J Shenyang Pharm Univ, 2015, 32(11): 853
[9] JIN PF, LIANG XL, XIA LF, et al. Determination of 20 trace elements and arsenic species for a realgar-containing traditional Chinese medicine Niuhuang Jiedu tablets by direct inductively coupled plasma-mass spectrometry and high performance liquid chromatography-inductively coupled plasma-mass spectrometry[J].J Trace Elem Med Biol, 2016, 33: 73
[10] 张炜, 刘学良, 骆桂法, 等. 佐太等珍宝矿物类藏药材中总砷、总汞及可溶性砷汞含量的对比研究[J].药物分析杂志, 2016, 36(4): 721
ZHANG W, LIU XL, LUO GF, et al. Comparative study of total and soluble arsenic, mercury in the Tsothel and other precious Tibetan medicines[J].Chin J Pharm Anal, 2016, 36(4): 721
[11] 刘敏敏, 陈浩桉, 肖秀春, 等. 原子荧光法测定甘草及甘草制剂中砷含量及不同消解方法比较[J].药物分析杂志, 2016, 36(7): 1274
LIU MM, CHEN HA, XIAO XC, et al. Determination of arsenic in Glycyrrhizae Radix et Rhizoma and its preparations by atomic fluorescence spectrometry and comparison of different digestion methods[J].Chin J Pharm Anal, 2016, 36(7): 1274
[12] 王任, 吴鸳鸯, 周明昊, 等. 原子荧光法测定并比较4种金枪鱼背部肉中硒的含量[J].药物分析杂志, 2017, 37(10): 1871
WANG R, WU YY, ZHOU MH, et al. Comparison of selenium content in four kinds of tuna back meat by atomic fluorescence spectrometry[J].Chin J Pharm Anal, 2017, 37(10): 1871
[13] 郭腾, 施峰, 杨刚, 等. 固体分散体技术对纳米雄黄稳定性及体外溶出的影响研究[J].中国中药杂志, 2013, 38(17): 2782
GUO T, SHI F, YANG G, et al. Effect of stability and dissolution of realgar nano-particles using solid dispersion technology[J].China J Chin Mater Med, 2013, 38(17): 2782
[14] WU JZ, HO PC. Evaluation of the in vitro activity and in vivo bioavailability of realgar nanoparticles prepared by cryo-grinding[J].Eur J Pharm Sci, 2006, 29(1): 35
[15] 宋晓妮, 陆宇婷, 杨丹亿, 等. 大鼠灌胃朱砂与复方牛黄消炎胶囊后汞的药代动力学研究[J].中国中药杂志, 2017, 42(14): 2779
SONG XN, LU YT, YANG DY, et al. Pharmacokinetics of mercury after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule in rats[J].China J Chin Mater Med, 2017, 42(14): 2779
