Objective: To establish an UPLC-MS/MS method for the simultaneous determination of seven main pyrrolizidine alkaloids (imtermedine, lycopsamine, rinderine, rinderine N-oxide, imtermedine N-oxide and lycopsamine N-oxide and senkirkine) in Cirsii Japonici Herba, and to carry out preliminary risk assessment according to the research results. Methods: The assay was performed on an ACQUITY UPLC HSS T3 column (100 mm×2.1mm, 1.8 μm) and the sample was eluted with a gradient mobile phase consisting of 0.05% formic acid and 2.5 mmol·L-1 ammonium formate in water (A)-0.05% formic acid and 2.5 mmol·L-1 ammonium formate in acetonitrile (B). The MS system was operated by using electrospray ionization (ESI) in the positive ion mode, and the scan mode was in multiple reactions monitoring (MRM) mode. External standard method was used in the experiment. Results: The linear ranges of imtermedine, lycopsamine, rinderine, rinderine N-oxide, imtermedine N-oxide and lycopsamine N-oxide and senkirkine were 1.024-102.4, 1.032-103.2, 1.016-101.6, 1.022-102.2, 1.056-105.6, 0.958-95.8 and 0.988-98.8 ng·mL-1, respectively (r>0.999 0). The average recoveries were 89.2%, 95.2%, 88.6%, 92.1%, 106.2%, 91.5% and 93.2% with RSD of 3.2%, 3.5%, 3.1%, 3.8%, 3.2%, 3.3% and 3.9%, respectively. The content ranges of the above-mentioned 7 pyrrolizidine alkaloidsin the 10 batches of Cirsii Japonici Herba were 1.36-5.32,1.38-5.25, 1.12-5.84, 1.69-8.52, 3.03-25.25, 1.25-5.96 and 1.29-4.25 μg·kg-1, respectively. Conclusion: The method can be used for the determination of 7 pyrrolizidine alkaloids in Cirsii Japonici Herba, providing a scientific basis for the quality evaluation and safe medication of this herb.
ZAN Ke, LI Yao-lei, ZHOU Ying, ZUO Tian-tian, JIN Hong-yu, WANG Ying, MA Shuang-cheng
. Determination and preliminary risk assessment of seven main pyrrolizidine alkaloids in Cirsii Japonici Herba by UPLC-MS/MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(10)
: 1690
-1696
.
DOI: 10.16155/j.0254-1793.2021.10.04
[1] 高江国, 王长虹, 李岩, 等. 吡咯里西啶生物碱的药理作用、毒性及药(毒)物代谢动力学研究进展[J].中国中药杂志, 2009, 34(5): 506
GAO JG, WANG CH, LI Y, et al. Advance on pharmacologic actions,toxicity and pharmacokinetics of pyrrolizidine alkaloids[J].China J Chin Mater Med, 2009, 34(5): 506
[2] 汤俊,程敏. 紫草中的吡咯里西啶类成分及其代谢毒性研究进展[J].药学学报, 2019, 54(3): 420
TANG J, CHENG M. Recent progress in the research on pyrrolizidine alkaloids from Chinese medicinal herb "Zicao" and their metabolic toxicity[J].Acta Pharm Sin, 2019, 54(3): 420
[3] 郭严,张世荣,文良志, 等. 我国吡咯烷生物碱致肝窦阻塞综合征的临床特征分析[J].临床肝胆病杂志, 2018, 34(6): 1277
GUO Y, ZHANG SR,WEN LZ, et al. Clinical features of sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids in China[J].J Clin Hepatol ,2018, 34(6): 1277
[4] 汤俊,服部征雄. 《中国药典》含吡咯里西啶生物碱的中药品种与用药安全[J].药学学报, 2011, 46(7): 762
TANG J, HATTORI M. Pyrrolizidine alkaloids-containing Chinese medicines in the Chinese Pharmacopoeia and related safety concerns[J].Acta Pharm Sin, 2011, 46(7): 762
[5] ZHOU N, LI N, CHOI FF, et al. A new approach for simultaneous screening and quantification of toxicpyrrolizidine alkaloids in some potential pyrrolizidine alkaloid-containing plants by using ultra performance liquid chromatography-tandem quadrupolemass spectrometry[J].Anal Chim Acta, 2010, 681(1-2): 33
[6] LUO ZM, LI X, WANG L, et al. Development of UPLC-Q-TOF-MS coupled with cation-exchange solid-phase extraction method for the determination of ten pyrrolizidine alkaloids in herbal medicines[J]. Anal Sci, 2019, 35(10): 1317
[7] 中华人民共和国药典2020年版. 一部[S]. 2020: 26
ChP 2020. VolⅠ[S]. 2020:26
[8] Ministry of Health. PRC: Notice of the Ministry of Health on Further Standardizing the Management of Health Food Raw Materials[R/OL]. [2002-3-11]. http://www.nhc.gov.cn/wjw/gfxwj/201304/e33435ce0d894051b15490aa3219cdc4.shtml.
[9] 中国植物志编辑委员会. 中国植物志. 第74卷. 第1分册[M]. 北京: 科学出版社, 1987: 103
Editorial Committee of Flora of China. Flora of China. Vol. 74. Part 1[M]. Beijing: Science Press, 1987: 103
[10] ZHAO Y, QIU MY, LIU YT, et al. Research progress on chemical constituents and pharmacological of Cirsium japonicum[J].Chin Tradit Herb Drugs, 2017, 48(21): 4584
[11] WANG JC, ZHANG M, CHEN LH, et al. Determination of toxic pyrrolizidine alkaloids in traditional Chinese herbal medicines by UPLC-MS/MS and accompanying risk assessment for human health[J].Molecules, 2021, 26(6): 1648
[12] 王涛,宋海波. 吡咯里西啶类生物碱肝毒性研究进展及风险分析[J].医药导报, 2018, 37(9): 1033
WANG T, SONG HB. Research progress and risk analysis on hepatotoxicity of pyrrolizidine alkaloids[J].Her Med, 2018, 37(9): 1033
[13] SCHRENK D, GAO L, LIN G, et al. Pyrrolizidine alkaloids in food and phytomedicine: occurrence, exposure, toxicity, mechanisms, and risk assessment-a review[J].Food Chem Toxicol, 2020, 136: 111107
[14] 孙潇翔,向娥,邱帅凯, 等. 吡咯里西啶生物碱毒性作用研究进展[J].中国药物警戒, 2019, 16(2): 76
SUN XX, XIANG E, QIU SK, et al. Research progress on toxicity of pyrrolizidinealk aloids[J].Chin J Pharmacovigil, 2019, 16(2): 76
[15] European Medicines Agency. Public Statement on Contamination of Herbal Medicinal Products/Traditional Herbal Medicinal Products with PyrrolizidineAlkaloids[R/OL]. [2016-5-31]. http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2016/06/WC500208195.pdf
