OBJECTIVE To establish an LC-MS/MS method for determination of atractylenolide Ⅰ, atractylenolide Ⅱ and atractylenolide Ⅲ in rat plasma, and study the pharmacokinetics of the three active components of Atractylodes Rhizoma-Cyperus Rhizoma extract in rats. METHODS Diphenhydramine was used as the internal standard, and the plasma samples were treated by liquid-liquid extraction with ethyl acetate. ACQUITY UPLC BEH-C18 column (2.1 mm×50 mm, 1.7 μm) was used, and acetonitrile-0.05% formic acid water was used as the mobile phase. Positive ion scanning was carried out by electrospray ion source (ESI). Multiple reaction monitoring (MRM) was used to monitor precursor to product ion transition of m/z 231.2→185.1 for atractylenolide I, m/z 233.2→187.1 for atractylenolide Ⅱ, m/z 249.2→231.1 for Ⅲ, and m/z 256.2→167.1 for IS (diphenhydramine). Pharmacokinetic parameters were calculated by DAS 3.3.2 software. RESULTS The linear ranges of atractylenolide Ⅰ, atractylenolide Ⅱ and atractylenolide Ⅲ were 0.315 0-20.00, 0.315 0-20.00 and 3.150-200.0 ng mL-1, respectively. Indicators of the method validation were in line with requirements. The drug concentration-time curves of the three active components of the extract showed double peaks, and the pharmacokinetic parameters were as follows: t1/2: (12.593±3.27) (14.868±5.51) (9.736±4.08) h, tmax: (0.458±0.29) (0.389±0.13) (0.347±0.08) h, ρmax: (7.719±4.93) (13.43±3.50) (153.702±23.51) ng·mL-1, AUC0-t: (42.592±19.45) (64.132±15.12) (1 042.156±168.43) ng·h·mL-1. CONCLUSION The LC-MS/MS method is simple and sensitive and can be used to study the pharmacokinetics of Atractylodes Rhizoma-Cyperus Rhizoma extract in rats.
Key words
Atractylodes Rhizoma-Cyperi Rhizoma drug pair /
atractylenolide /
pharmacokinetics /
LC-MS/MS
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References
[1] JI S L, LU S J, ZHENG L, et al. A study on network pharmacological mechanism of Cangzhu-Xiangfu in treating polycystic ovary syndrome. Clin J Chin Med(中医临床研究), 2022, 14(32):109-114.
[2] LI X Q, GE R, WANG Y Q, et al. Effect of Yueju pill on CREB target gene expression in hippocampus of mice. Lishizhen Med Mater Med Res(时珍国医国药), 2021, 32(6):1313-1315.
[3] GU Y Y. Clinical study of Cangfu Dao Tan Decoction combined with cupping therapy on ovulation disorder of sterility of phlegm-dampness polycystic ovary syndrome. Nanjing:Nanjing University of Chinese Medicine, 2022.
[4] PANG H M, YAO Y, DU P. Analysis on the characteristics of menstrual period drug use in the treatment of infertility by Professor Xia Guicheng. China Med Her(中国医药导报), 2021, 18(16):129-132, 136.
[5] ZHOU T Y, SUI J, MENG Y X. Systematic evaluation and sequential analysis of clinical efficacy of Cangfu Daotan Pills in the treatment of polycystic ovary syndrome. Lishizhen Med Mater Med Res(时珍国医国药), 2022, 33(5):1235-1241.
[6] WANG Y, ZHANG M M, JIANG H X. Application of drug pairs in amenorrhea. Henan Tradit Chin Med(河南中医), 2021, 41(11):1639-1642.
[7] PAN L W, SONG J. Study on inhibiting effects of atractylenolide against melanoma in vitro and in vivo. Chin J Hosp Pharm(中国医院药学杂志), 2015, 35(8):682-685.
[8] MA Z M, LAI S L, ZHU J Y, et al. Atractylenolide Ⅰ improves acetaminophen-induced acute liver injury in mice by inhibiting MAPK/NF-KB signaling pathway. China J Chin Mater Med(中国中药杂志), 2022, 47(4):1017-1023.
[9] DOU S, YANG C, ZOU D, et al. Atractylenolide Ⅱ induces cell cycle arrest and apoptosis in breast cancer cells through ER pathway. Pak J Pharm Sci, 2021, 34(4):1449-1458.
[10] YUAN M Y, ZHANG X X, XIE X D, et al. Observation on effect of atractylodesin Ⅱ on gastric cancer cells based on macrophage polarization. Chin J Exp Tradit Med Form(中国实验方剂学杂志), 2020, 26(21):100-108.
[11] ZHOU Y, HUANG S, WU F, et al. Atractylenolide Ⅲ reduces depressive-and anxiogenic-like behaviors in rat depression models. Neurosci Lett, 2021, 759:136050.DOI: 10.1016/j.neulet.2021.136050.
[12] WANG F X. Effect of atractenolactone Ⅲ on aging of hepatic stellate cells induced by regulation of glutamine metabolism on anti-hepatic fibrosis mechanism. Nanjing:Nanjing University of Chinese Medicine, 2022.
[13] YAN X L. YU Y D, YANG D D. Clinical efficacy of acupuncture combined with modified Xiangfu Decoction in treatment of menopausal insomnia cause by liver Qi stagnation. China J Chin Mater Med(中国中药杂志), 2020, 45(6):1460-1464.
[14] GUO H L, DONG N F, HU L J, et al. Recognition of main anti-dysmenorrhea effect components in Cyperi Rhizoma based on constituents knock-out strategy. Chin J Exp Tradit Med Form(中国实验方剂学杂志), 2017, 23(10):7-11.
[15] HAI L N, WANG P F, WANG J H, et al. Study on the UPLC fingerprint and determination of six components of compound kushen injection. Chin Pharm J(中国药学杂志), 2022, 57(14):1198-1204.
[16] WAN Y, SHEN Y M, ZOU J F, et al. The intestinal absorption characteristics of five active components in Lizhong Decoction. Acta Pharm Sin(药学学报), 2021, 56(6):1689-1695.
[17] ZHOU S N, WU S H, SUN Z, et al. Metabolites and metabolic pathway analysis of atractylenolide l in rats based on UHPLC-O-Orbitrap HRMS. J Shenyang Pharm Univ(沈阳药科大学学报), 2022. https://doi.org/10.14066/j.cnki.cn21-1349/r.2022.0638.
[18] ALMAZROO OA, MIAH MK, VENKATARAMANAN R. Drug metabolism in the liver. Clin Liver Dis, 2017, 21(1):1-20.
[19] ZANGER UM, SCHWAB M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther, 2013, 138(1):103-141.
[20] YUAN J, WEI F, LUO X, et al. Multi-component comparative pharmacokinetics in rats after oral administration of fructus aurantii extract, naringin, neohesperidin, and naringin-neohesperidin. Front Pharmacol, 2020, 11:933. DOI:10.3389/fphar.2020.00933.
[21] DURNIK R, SINDLEROVA L, BABICA P, et al. Bile acids transporters of enterohepatic circulation for targeted drug delivery. Molecules, 2022, 27(9):2961. DOI: 10.3390/molecules27092961.
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