Pharmacokinetic Study of Araloside A in Rats Based on LC-MS/MS Techniques
GUO Dong-yan1,2, ZHAI Bing-tao2, SHI Ya-jun1,2, FAN Yu2, WANG Lu1,2, WANG Mei2
1. Shaanxi Key Laboratory of Basic and New Herbal Medicament Research, Xianyang 712046,China; 2. The Medicine College of Shaanxi University of Chinese Medicine, Xianyang 712046, China
Abstract��OBJECTIVE To develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties of araloside A. METHODS Araloside A was administered in a dose of 50 mg��kg-1 via gastric in fusion and 5 mg��kg-1 by intravenous injection in rats.Araloside A was analyzed by a validated LC-MS/MS method in plasma after intravenous and intragastric administration. The pharmacokinetic parameters were evaluated by software DAS 3.0. RESULTS The RESULTS of pharmacokinetic study showed that the linear range of araloside A was good in 1.0-10 000.0 ��g��L-1(r>0.994 8). The specificity, precision and accuracy, matrix effect and extraction recovery rate and stability all meet the requirements. The main pharmacokinetic parameters for intragastric administration with araloside A 50 mg��kg-1 and intravenous injection of araloside A 5 mg��kg-1 were as follows:t1/2 was(8.65��3.22) and(2.00��0.21)h, AUC0-t was(277.14��101.00) and (21 194.59��4 385.13)ng��h��L-1, MRT0-t was (7.88��0.64) and (1.21��0.11)h, Vd/F was (2 229.99��1 013.97) and (0.71��0.20)L��kg-1, CL/F was(149.11��62.28) and (0.24��0.05) L��h-1��kg-1, respectively; ��max was (32.68��10.74) ��g��L-1 for intragastric administration and tmax reached(1.21��0.70) h, oral bioavailability of araloside A was about 0.14%. CONCLUSION The LC-MS/MS method established is specific and sensitive, and can be successfully applied in basic pharmacokinetic study of araloside A in rat plasma.
������, �Ա���, ʷ�Ǿ�, ���, ��¶, ����. ����LC-MS/MS̽�֘Bľ����A�ڴ������ڵ�ҩ��ѧ����[J]. �й�ҩѧ��־, 2018, 53(7): 538-543.
GUO Dong-yan, ZHAI Bing-tao, SHI Ya-jun, FAN Yu, WANG Lu, WANG Mei. Pharmacokinetic Study of Araloside A in Rats Based on LC-MS/MS Techniques. Chinese Pharmaceutical Journal, 2018, 53(7): 538-543.
FAN Y,GUO D Y,SONG Q,et al. Advances on pharmacology effect of Aralia taibaiensis and its active composition [J]. Mod J Int Tradit Chin West Med(�ִ�����ҽ�����־),2014,23(4):221-222.
[2]
LEE E B, KIM O J,KANG S S,et al. Araloside A,an antiulcer constituent from the root bark of Aralia elata[J]. Bio Pharm Bull,2005,28(3):523-526.
[3]
LIU Y,LIU J F,LIU Z H,et al. The antitumor effects of Araloside A extracted from the root bark of Aralia elata on human kidney cancer cell lines[J]. Afr J Pharm Pharmacol,2011,5(4):462-467.
[4]
HONG L J. Studies on the antidiabetic saponin constituents of Aralia chinensis and Aralia taibaiensis[D]. Xi��an:Fourth Military Medical University,2012.
[5]
QIAN L N. Study on lipid solubility of Panax japonicus [D]. Wuhan:Wuhan Polytechnic University,2009.
[6]
SAORI T,KAZUYUKI H,MIKA H,et al. Inhibition of human rennin activity by saponins [J]. Biomed Res,2010,31(2):155-159.
[7]
ISKENDEROV G B. The metabolism of araloside A [J]. Farmakol Toksikol,1991,54(6):33-35.
[8]
QI D,YANG X,CHEN J,et al. Determination of chikusetsusaponin V and chikusetsusaponin �� in rat plasma by liquid chromatography-mass spectrometry and its application to a preliminary pharmacokinetic study [J]. Biomed Chromatogr,2013,27(11):1568-1573.
[9]
ZHU H,DING L,SHAKYA S,et al. Simultaneous determination of asperosaponin �� and its active metabolite hederagenin in rat plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in pharmacokinetic study [J]. J Chromatogr B Analyt Technol Biomed Life Sci,2011,879(30):3407-3414.
[10]
WU C,MA P,LI P F,et al. LC-MS/MS determination of oral bioavailability of akebia saponin D in rat [J]. J Beijing Norm Univ(Nat Sci)(����ʦ����ѧѧ����Ȼ��ѧ��),2014,50(1):62-65.
[11]
LIU E W,WANG J L,HAN L F,et al. Pharmacokinetics study of asperosaponin �� and its metabolites cauloside A,HN saponin F and hederagenin [J]. J Nat Med,2014,68(3):488-497.
[12]
XU Z Y. Studies on Pharmacokinetics and metabolic mechanism of Timosaponin B-��[D]. Shanghai:Second Military Medical University,2013.
[13]
YANG Q Y,KANG L,GU S,et al. Pharmacokinetics studies of ginsenoside Rb1 in rats[J]. Chin Pharm J(�й�ҩѧ��־),2014,49(3):221-226.
[14]
FENG X J,WANG M X,FENG Z Y,et al. Pharmacokinetic study of Matrine Injection in rats with different administration ration routes by LC-MS/MS method[J]. Chin Pharm J(�й�ҩѧ��־),2017,52(4):303-307.
[15]
YAN L,YANG X L,MENG Z Q,et al. Simultaneous quantification of akebia saponin D and its five metabolites in human intestinal bacteria using ultra-performance liquid chromatography triple quadrupole mass spectrometry [J]. J Chromatogr B Analyt Technol Biomed Life Sci,2014,971(15):81-88.
[16]
HE W, DONG H Y. Applicationg of weighted least square method in the prediction of physiological pharmacokinetics [J]. Chin J Clin Rat Drug Use(�ٴ�������ҩ��־),2011,4 (11C):110-111.
[17]
HU L L. Quantitative Analysis, Preclinical pharmacokinetics and Tissue distribution of Rhychophylline in Biological Matrix [D]. Chognqing:Third Military Medical University,2013.