Safety Monitoring

Simultaneous determination of eight aconitum alkaloids in Shenkangning capsules by UPLC-MS/MS assisted by solid phase extraction*

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  • 1. Institute of Chinese Materia Medica, Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203,China;
    2. Jiangxi Puzheng Pharmaceutical Co., Ltd., Ji'an 331409, China

Received date: 2021-03-13

  Online published: 2024-06-24

Abstract

Objective: To establish a method for determination of aconitine alkaloids in Shenkangning capsules. Methods: The determination was performed on a Waters ACQUITY UPLC HSS T3 column (2.1 mm×100 mm,1.8 μm). The mobile phase was consisted of 0.1% formic acid solution (A)-acetonitrile (B) in gradient elution, the flow rate was 0.3 mL·min-1 and the column temperature was 40 ℃. The analytes were determined by electrospray ionization source (ESI) combined with multiple reaction monitoring (MRM) in positive ion mode. To establish a SPE-UPLC-MS/MS method for the determination of aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, benzoylmesaconine, aconine and mesaconine in Shenkangning capsules. Results: Aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, benzoylmesaconine, aconine and mesaconine showed good linearities in the ranges of 0.31-99.80, 0.78-99.80, 0.31-75.15, 30.31-485.00, 309.38-3 712.50, 61.88-742.50, 7.75-248.00, and 61.25-1 960.00 ng·mL-1, respectively. The RSDs of the precision, repeatability and stability tests were below 5%. The average recoveries were in the range of 80.6%-109.0%. The contents of mesaconitine, benzoylaconine, benzoylhypaconine, benzoylmesaconine, aconine and mesaconine in 12 batches of Shenkangning capsules were 0.002-0.041, 1.163-1.758, 9.300-16.446, 2.070-3.112, 0.166-0.319, and 1.243-3.067 μg per capsule, respectively. Conclusion: The method is stable and reliable, and can be used for quality control of Shenkangning capsules.

Cite this article

LIU Shi-xin, CHEN Liang-ni, CHENG Xue-mei, JI Li-li, LI Xiao-feng, LIU Sheng, KANG Xing-dong, WEI Xiao-hui, WANG Chang-hong . Simultaneous determination of eight aconitum alkaloids in Shenkangning capsules by UPLC-MS/MS assisted by solid phase extraction*[J]. Chinese Journal of Pharmaceutical Analysis, 2022 , 42(2) : 302 -311 . DOI: 10.16155/j.0254-1793.2022.02.15

References

[1] 中华人民共和国药典2020年版.一部[S].2020: 1131
ChP 2020. Vol Ⅰ [S].2020: 1131
[2] 刘如品,宋敏,刘玉琴, 等.肾康宁胶囊治疗慢性肾功能衰竭的临床观察[J].中国药业, 2005,14 (11): 73
LIU RP, SONG M, LIU YQ, et al.Clinical observation of Shenkangning capsule in the treatment of chronic renal failure [J].China Pharm, 2005, 14(11): 73
[3] 廖佐芹,黄居森,严金玲, 等.自拟白马大黄汤灌肠配合肾康宁胶囊治疗慢性肾衰竭30例临床疗效观察及小鼠急性毒性实验报告[J].赣南医学院学报, 2007, 27 (4): 512
LIAO ZQ,HUANG GS,YAN JL, et al.Clinical observation on 30 cases of chronic renal failure treated by self-made Baima Dahuang Decoction enema combined with Shenkangning capsule and experimental report on acute toxicity in mice [J].J Gannan Med Univ, 2007, 27 (4): 512
[4] 吴瑞艳,崔淑华,张悦, 等.肾康宁胶囊与花粉及南瓜籽制剂联合微量元素制剂治疗肾阳虚证的临床疗效[J].临床合理用药杂志, 2019, 12(33): 56
WU RY, CUI SH, ZHANG Y, et al.Clinical efficacy of Shenkangning capsule, pollen and pumpkin seed preparation combined with trace element preparation in the treatment of kidney yang deficiency syndrome [J].Chin J Clin Rational Drug Use, 2019, 12(33): 56
[5] 李军,张义军.肾康宁胶囊联合坎地沙坦治疗糖尿病早期肾病临床疗效观察[J].中国医疗设备, 2017, 32(S1): 99
LI J, ZAHNG YJ. Clinical observation of kidney Corelle capsule combined with candesartan in treatment of early diabetic nephropathy [J].Chin Med Dev, 2017, 32(S1): 99
[6] 李燕, 李芸霞, 袁岸, 等. “药材-提取物-成分”追踪附子强心作用物质基础[J].中药与临床, 2016,7(5):54
LI Y, LI YX, YUAN A, et al.Exploration of the material basis for cardiotonic effect of Fuzi under the guidance “Herb-Extract-Ingredient” [J].Pharm Clin Chin Mater Med, 2016, 7(5):54
[7] 王璐, 丁家昱, 刘秀秀, 等. 附子中胺醇型二萜生物碱的鉴定及其强心活性研究[J].药学学报, 2014, 49 (12): 1699
WANG L, DING JY, LIU XX, et al.Identification of aminoalcohol-diterpenoid alkaloids in Aconiti Lateralis Radix Praeparata and study of their cardiac effects[J].Acta Pharm Sin, 2014, 49 (12): 1699
[8] 张思齐, 李延飞, 李新明. 附子中单酯型生物碱类成分靶向ACE2-Ang1-7轴治疗慢性心力衰竭的研究进展[J].科技视界, 2019, 9(23): 212
ZHANG SQ, LI YF, LI XM. The recent advances about targeting the ACE2-Ang (1-7)-MAS receptor axis in the treatment to heart failure by monoester alkaloids of aconite were summarized[J].Sci Technol View, 2019, 9(23): 212
[9] 熊秋韵, 李梦婷, 缪璐琳, 等. 附子不同炮制品抗炎、镇痛和提高免疫功能作用的比较研究[J].中药药理与临床, 2017, 33(1): 123
XIONG QY, LI MT, LIAO LL, et al.Comparative study of different processed products of AconitiLateralis Radix Praeparata on effects of anti-inflammation, analgesia and enhancing immune function[J].Pharmacol Clin Chin Mater Med, 2017, 33(1): 123
[10] 徐红萌, 姜慧卿. 附子对神经病理性疼痛大鼠的镇痛作用[J].中华麻醉学杂志, 2005, 25(5): 381
XU HM, JIANG HQ. Analgesic effect of processed Aconiti tuber in rats with neuropathic pain[J].Chin J Anesthesiol, 2005, 25(5): 381
[11] 田劭丹, 刘雪强, 王笑民, 等. 乌头碱影响KBV200细胞Pgp蛋白表达的组化实验[J].中华中医药学刊, 2006, 24(1): 55
TIAN SD, LIU XQ, WANG XM, et al.The immunohistochemistry experiment of the Pgp protein expression rate of kbv200 cell line affected by myoctonine[J].Chin Arch Tradit Chin Med, 2006, 24(1): 55
[12] 谢晓芳. 附子心脏毒作用机制研究[D].成都: 成都中医药大学, 2012
XIE XF. Study on the Mechanism of Cardiotoxicity of Radix Aconiti Lateralis Praeparata [D].Chengdu:Chengdu University of Chinese Medicine, 2012
[13] 潘校琦, 彭成. 附子神经毒性研究进展[J].世界中医药, 2017, 12(11): 2551
PAN XQ, PENG C. Research progress on neurotoxicity of radix aconiti lateralis praeparata[J].World Chin Med, 2017, 12(11): 2551
[14] 肖凯, 李宏霞, 王亚其, 等. 乌头类中药的胚胎毒性及致畸性[J].中国药科大学学报, 2005, 36(6): 567
XIAO K, LI HX, WANG YQ, et al. Embryotoxicity and teratogenecity of aconitum in rats[J].J Chin Pharm Univ, 2005, 36(6): 567
[15] 郝丽丽, 梁国欣, 魏洪鑫, 等. 中药附子的毒理学安全性研究进展[J].毒理学杂志, 2020, 34(6): 435
HAO LL, LIANG GX, WEI HX, et al. Advances in toxicological security of FUZI one of the Chinese traditional medicinal crops[J].J Toxicol, 2020, 34(6): 435
[16] 杨雪,夏东胜,田春华, 等.508例附子不良反应文献分析[J].中国药物警戒, 2017, 14(10): 615
YANG X, XIA DS, TIAN CH, et al.Lite rature analysis of 508 cases reports of adverse reactions induced by Aconiti Lateralis Radix praeparata [J].Chin J Pharmacov, 2017, 14(10):615
[17] 黄勤安, 张聿梅, 何轶, 等. 乌头碱水解转化规律的研究[J].中国中药杂志, 2007, 32 (20): 2143
HUANG QA, ZHANG YM, HE Y, et al.Studies on hydrolysis of aconitine[J].Chin J Chin Mater Med, 2007, 32 (20): 2143
[18] 袁圆,王晓明,潘桂湘, 等. LC-MS/MS测定16种市售中药制剂中8个乌头类生物碱的含量[J].时珍国医国药, 2015, 26(12): 2823
YUAN Y, WANG XM, PAN GX, et al.Determination of 8 alkaloids in Aconitum species of Chinese traditional patent medicine by LC-MS/MS [J].Lishizhen Med Chin Mater Med Res, 2015, 26(12): 2823
[19] 张聿梅,何轶,李耀磊, 等. 高效液相色谱与QDA质谱联用同时测定附子理中丸中6个单酯及双酯型生物碱含量[J].药物分析杂志, 2018,38(7):1248
ZAHNG YM, HEI Y, LI YL, et al.Simultaneous determination of six diterpenoid alkaloids in Fuzilizhong pills were determined by HPLC coupled with QDA mass detector[J].Chin J Pharm Anal, 2018, 38(7): 1248
[20] 唐进法,张书琦,王晓艳, 等. HPLC-MS/MS多组分含量测定研究附子配方颗粒的质量一致性[J].中国中药杂志,2018,43(9):1871
TANG JF, ZAHNG SQ, WANG XY, et al.Quality consistency evaluation of Fuzi formula granules using determination of multi-component contents by HPLC-MS/MS method[J].China J Chin Mater Med, 2018, 43(9): 1871
[21] GUO N,YANG DW, KEYUME A, et al.Simultaneous quantitation of seven alkaloids in processed Fuzi decoction by rapid resolution liquid chromatography coupled with tandem mass spectrometry.[J].J Sep Sci, 2013, 36(12): 1953
[22] 史煜华, 黄文康, 黄琴伟, 等. SPE-HPLC测定风湿骨痛片中6种生物碱类物质的含量[J].中国现代应用药学, 2018, 35(12): 1797
SHI YH, HUANG WK, HUANG QW, et al.Content determination of six alkaloids in Fengshigutong tablet by SPE-HPLC[J].Chin J Mod Appl Pharm, 2018, 35(12): 1797
[23] 郑琴, 陆浩伟, 郝伟伟, 等. 乌头类双酯型生物碱水解转化规律及含量计算方法研究[J].中国药学杂志, 2011, 46(9): 652
ZHENG Q, LU HW, HAO WW, et al.Study on hydrolysis of aconitum alkaloids and quantitative analysis method of their hydrolysates[J].Chin Pharm J, 2011, 46(9): 652
[24] 张小龙, 吴先富, 王昆, 等. HPLC-QTOF-MS 法测定风湿骨痛胶囊中9个乌头类生物碱的含量[J].药物分析杂志, 2015, 35(3): 414
ZHANG XL, WU XF, WANG K, et al.Determination of 9 aconitum alkaloids in Fengshi Gutong capsules by HPLC-QTOF-MS[J].Chin J Pharm Anal, 2015,35(3): 414
[25] 曾丽华, 伍振峰, 王芳, 等. 中药制剂质量均一性的现状问题及保证策略研究[J].中国中药杂志, 2017, 42(19): 3826
ZENG LH, WU ZF, WANG F, et al. Status, problems and warranty strategy of quality uniformity for traditional Chinese medicine preparations[J].China J Chin Mater Med, 2017, 42(19): 3826
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