Abstract��OBJECTIVE To develop an LC-MS/MS method for the quantitative analysis of ocotillol in rat plasma, and study the pharmacokinetic characteristics of ocotillol in rats after oral administration.METHODS Ocotillol was extracted from plasma sample by protein precipitation. The concentration of ocotillol in plasma was determined by LC-MS/MS and the plasma concentration-time curve and main pharmacokinetic parameters were calculated after a single oral administration of ocotillol at 40 mg��kg-1 to SD rats.RESULTS Excellent linearity was found between 10-240 ng��mL-1. Intra-and inter-day precision values (RSDs) of QC samples were both below 15% and the extraction recoveries of ocotillol from plasma were higher than 84.14%. Double peaks were observed in the mean plasma concentration versus time profile of ocotillol after oral administration. The main pharmacokinetic parameters of ocotillol were as follows:the mean maximum plasma concentration (��max) was (156.60��51.84) ng��mL-1 occurring at (0.83��0.26) h post dose, the mean elimination half-time (t1/2) was (8.82��7.56) h, and the mean area under the plasma concentration versus time curve (AUC0-t) was (687.15��144.08) ng��h��mL-1.CONCLUSION The current data shows that ocotillol is rapidly absorbed in rats after oral administration and slowly eliminated from circulatory blood system, with low plasma exposure. Enterohepatic circulation may contribute to the atypical drug absorption profiles.
�����,�����,������,������,�⾩ѧ,����Ӣ,��ɯ,����. �������÷��о��¿���¡������Ԫ�ڴ������ڵ�ҩ������ѧ��Ϊ[J]. �й�ҩѧ��־, 2018, 53(9): 749-754.
LI Zhen-guo, GAO Ze-bin, GONG Ai-hua, LI Xiao-lan, WU Jing-xue, ZHANG Long-ying, YU Sha, GENG Cong. Pharmacokinetic Study of Ocotillol in Rats by LC-MS/MS. Chinese Pharmaceutical Journal, 2018, 53(9): 749-754.
FU X Y, KONG L, TANG M T, et al. Protective effect of ocotillol against doxorubicin-induced acute and chronic cardiac injury [J] . Mol Med Rep, 2014, 9(1):360-364.
[2]
WANG Z J, SUN L Q, PENG W B, et al. Ginseng derivative ocotillol enhances neuronal activity through increased glutamate release:a possible mechanism underlying increased spontaneous locomotor activity of mice [J] . Neuroscience, 2011, 195:1-8.
[3]
WANG H B, YU P F, BAI J, et al. Ocotillol enhanced the antitumor activity of doxorubicin via p53-dependent apoptosis [J] . Evid Based Complement Alternat Med, 2013, 2013:468-537.
[4]
PENG M, LI X N, ZHANG T, et al. Stereoselective pharmacokinetic and metabolism studies of 20(S)-and 20(R)-ginsenoside Rg3 epimers in rat plasma by liquid chromatography-electrospray ionization mass spectrometry [J] . J Pharm Biomed Anal, 2016, 121:215-224.
[5]
WU H C, LIU H M, BAI J, et al. Simultaneous determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re and 20(S) protopanaxatriol in beagle dog plasma by ultra high performance liquid mass spectrometry after oral administration of a Panax notoginseng saponin preparation [J] . J Chromatogr B, 2015, 974:42-47.
[6]
GENG C, WU D, LV H Y, et al. Plasma protein binding characteristics of neopanaxadiol in rat by UPLC-MS/MS[J] . Chin Pharm J(�й�ҩѧ��־), 2017, 52(5):404-408.
[7]
WANG W Y, SHAO Y F, MA S S, et al. Determination of 20(S)-protopanaxadiol ocotillol type epimers in rat plasma by liquid chromatography tandem mass spectrometry[J] . J Chromatogr B, 2012, 887-888:19-24.
[8]
GAO H M, LI Z, LI P Y, et al. Determination of pseudoginsengenin DQ in rat plasma by UPLC-MS/MS and application of the method in a pharmacokinetic study[J] . J Chromatogr B, 2013, 933:1-7.
[9]
HUO J P, WANG H Y, HU P, et al. Determination of pseudo-ginsenoside GQ in human plasma by high performance liquid chromatography-tandem mass spectrometry[J] . Biomed Chromatogr, 2013, 27(12):1701-1707.
[10]
CHEN X J. Review on Pharmacokinetic(ҩ���л����ѧ�о���չ) [M] . Beijing:Chemical Industry Press, 2008:1-5.
[11]
LIPINSKI C A, LOMBARDO F, DOMINY B W, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings[J] . Adv Drug Deliv Rev, 2001, 46(1-3):3-26.
[12]
REN H C, SUN J G, WANG G J, et al. Sensitive determination of 20(S)-protopanaxadiol in rat plasma using HPLC-APCI-MS:application of pharmacokinetic study in rats[J] . J Pharm Biomed Anal, 2008, 48(5):1476-1480.
[13]
GENG C, LIU J H, GUAN Q X, et al. Validated LC-ESI-MS/MS method for the quantitation of neopanaxadiol:a novel neuroprotective agent from Panax ginseng and its application to a pharmacokinetic study in rat plasma [J] . Chromatographia, 2013, 76(9-10):509-514.
[14]
ZHAO J, SU C, YANG C P, et al. Determination of ginsenosides Rb1, Rb2, and Rb3 in rat plasma by a rapid and sensitive liquid chromatography tandem mass spectrometry method:application in a pharmacokinetic study [J] . J Pharm Biomed Anal, 2012, 64-65:94-97.