Simultaneous determination of liensinine, isoliensinine and neferine from seed embryo of Nelumbo nucifera Gaertn. in rat plasma by a rapid HPLC method and its application to a pharmacokinetic study

Ying Huang; Libo Zhao; Yun Bai; Ping Liu; Jialing Wang; Jizhou Xiang

doi:10.1055/s-0031-1296209

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2011; 61(6): 347-352
DOI: 10.1055/s-0031-1296209

Cardiac Drugs · Cardiac Stimulants · Coronary Drugs

Editio Cantor Verlag Aulendorf (Germany)

Simultaneous determination of liensinine, isoliensinine and neferine from seed embryo of Nelumbo nucifera Gaertn. in rat plasma by a rapid HPLC method and its application to a pharmacokinetic study

Ying Huang

¹WuXi AppTec Co., Ltd, Wuxi, P. R., China

,

Libo Zhao

²Department of Pharmacy, Peking University People’s Hospital, Beijing, P. R., China

,

Yun Bai

³Department of Pharmacology, Tongji Medical College of Huazhong Universtiy of Science and Technology, Wuhan, P. R., China

,

Ping Liu

³Department of Pharmacology, Tongji Medical College of Huazhong Universtiy of Science and Technology, Wuhan, P. R., China

,

Jialing Wang

³Department of Pharmacology, Tongji Medical College of Huazhong Universtiy of Science and Technology, Wuhan, P. R., China

,

Jizhou Xiang

³Department of Pharmacology, Tongji Medical College of Huazhong Universtiy of Science and Technology, Wuhan, P. R., China

› Author Affiliations

Abstract

A rapid and specific HPLC method has been developed and validated for the simultaneous determination of liensinine (CAS 2586-96-1), isoliensinine (CAS 6817-41-0) and neferine (CAS 2292-16-2) in rat plasma. The sample was prepared by a liquid-liquid extraction with diethyl ether and the recovery was above 80 % from the plasma for the three compounds. Chromatographic separation was achieved with a Hypersil BDS C₁₈ column (4.0 mm × 250 mm, particle size 5 μm). A mobile phase consisting of methanol : 0.2 M KH₂P0₄:0.2 M NaOH : Methylamine (71:17:12:0.002, v/v/v/v, pH 9.2-9.3) was slowly delivered at 0.8 ml/min in isocratic mode with a detection wave-length of 282 nm. The linearity of calibration curves were good (r > 0.999) in the concentration range of 0.031 -2.00 μg/ml. The lower limit of quantification can reach 0.03 μg/ml for the three compounds. The intra-day and inter-day variations estimated with QC samples were less than 8 % for the three tested concentration levels. This developed method was applied in the plasma pharmacokinetic study of total bisbenzylisoquinoline alkaloids (TAL) of the lotus flower (Lian Zi Xin) following a single oral and intravenous administration of TAL in rats.

Key words

HPLC - Isoliensinine - Liensinine - Neferine - Pharmacokinetics

Full Text

References

References
1 Chao TY, Chou YL, Young PT, Chou TQ. Studies on the alkaloids of embryo loti, Nelumbo nucifera Gaertn. I. Isolation and characterisation of liensinine. Sci Sin. 1962; 11: 215-9
2 Hsieh YY, Pan PC, Chen WC, Kao YS. Studies on the alkaloids of embryo loti, Nelembo nucifera Gaertn. IV. Total synthesis of liensinine. Sci Sin. 1964; 13: 2020-5
3 Hsieh YY, Chen WC, Kao YS. Studies on the alkaloids of embryo loti, Nelembo nucifera Gaertn. III. Absolute configuration of liensinine. Sei Sin. 1964; 13: 2018-9
4 Furukawa H. Studies on the alkaloids of Nelumbo nucifera Gaertn. NMR spectra of liensinine type alkaloids. Yakugaku Zasshi. 1966; 86: 883-6
5 Chinese Pharmcopeia, 2005. Division one: 193.
6 Qian JQ. Cardiovascular pharmacological effects of bisben-zylisoquinoline alkaloid derivatives. Acta Pharmacol Sin. 2002; 23: 1086-92
7 Li GR, Li XG, Lu FH. Effects of neferine on transmembrane potentials of guinea pig myocardium. Zhongguo Yao Li Xue Bao. 1989; 10: 406-10
8 Gu DF, Li XL, Qi ZP, Shi SS, Hu MQ, Liu DM et al. Blockade of HERG K⁺ channel by isoquinoline alkaloid neferine in the stable transfected HEK293 cells. Naunyn Schmiedebergs Arch Pharmacol. 2009; 380: 143-51
9 Zhou H, Jiang H, Yao T, Zeng S. Fragmentation study on the phenolic alkaloid neferine and its analogues with anti-Hrv activities by electrospray ionization tandem mass spectrometry with hydrogen/deuterium exchange and its application for rapid identification of in vitro microsomal metabolites of neferine. Rapid Commun Mass Spectrom. 2007; 2: 2120-8
10 Yu J, Hu WS. Effects of neferine on platelet aggregation in rabbits. Yao Xue Xue Bao. 1997; 32: 1-4
11 Feng Y, Wu J, Cong R, Wang C, Zong Y, Feng Z. The effect of neferine on foam cell formation by anti-low density lipoprotein oxidation. J Tongji Med Univ. 1998; 18: 134-6
12 Xiao JH, Zhang JH, Chen HL, Feng XL, Wang JL. Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice. Planta Med. 2005; 71: 225-30
13 Shen G, Liang A, Zhao Y, Cao C, Liu T, Li C et al. Interaction between four herb compounds and a western drug by CYP3A4 enzyme metabolism in vitro. Zhongguo Zhong Yao Za Zhi. 2009; 34: 1705-11
14 Cao JG, Tang XQ, Shi SH. Multidrug resistance reversal in human gastric carcinoma cells by neferine. World] Gastroenterol. 2004; 10: 3062-4
15 Pan Y, Cai B, Wang K, Wang S, Zhou S, Yu X et al. Neferine enhances insulin sensitivity in insulin resistant rats. J Ethno-pharmacol. 2009; 124: 98-102
16 Hu X, Zhang X, Cai H, Lou S, Yin W. Pharmacokinetics of liensinine in rabbits. Zhongguo Zhong Yao Za Zhi. 1992; 17: 622-4
17 Huang Y, Bai Y, Zhao L, Hu T, Hu B, Wang J et al. Pharmacokinetics and metabolism of neferine in rats after a single oral administration. Biopharm Drug Dispos. 2007; 28: 361-72
18 Zhao L, Wang X, Wu J, Jia Y, Wang W, Zhang S et al. Improved RP-HPLC method to determine neferine in dog plasma and its application to pharmacokinetics. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 857: 341-6
19 Chen Y, Fan G, Wu H, Wu Y, Mitchell A. Separation, identification and rapid determination of liensine, isoliensinine and neferine from embryo of the seed of Nelumbo nucifera Gaertn. by liquid chromatography coupled to diode array detector and tandem mass spectrometry. J Pharm Biomed Anal. 2007; 43: 99-104
20 Liu S, Wang B, Li XZ, Qi LF, Liang YZ. Preparative separation and purification of liensinine, isoliensinine and neferine from seed embryo of Nelumbo nucifera GAERTN using high-speed counter-current chromatography. J Sep Sci. 2009; 32: 2476-81
21 Zhao LB, Jin Y, Wang JL. Determination of three alkaloids in total alkaloids extracts from Lotus plumule by RP-HPLC. Zhongguo Zhong Yao Za Zhi. 2007; 32: 1768-70