Dauricine has a variety of pharmacological properties including anti-inflammatory, anti-arrhythmic, and antihypertensive effects as well as reversing multidrug resistance (MDR) of cancer cells. While its therapeutic application is increasing, its bioavailability of different administration routes has not been studied. In the present study, we developed and validated a liquid chromatography/electrospray ionization mass spectrometry method (LC-MS/MS). Using this method, we quantified dauricine in rat plasma after administration via intravenous (i.v.) injection, per oral (p.o.), and intraperitoneal injection (i.p.). Our results indicated that this method detected plasma dauricine with a good linearity in the range of 1.95–1000.00 ng/mL (r = 0.9997). The extraction method showed an average intra- and inter-day recovery of 98.21–104.35% and 98.0–103.58%, respectively. Dauricine showed a fast absorption and widespread distribution after administration in all three tested routes. After intravenous administration (2.5, 5.0, 10.0 mg/kg), the pharmacokinetics of dauricine exhibited a first-order kinetics. In addition, dauricine showed a slow elimination with a long half-life (t1/2z) and double peaks phenomenon following p.o. and i.p. administration. Furthermore, using area under the plasma concentration-time curve (AUC), we calculated absolute bioavailability, which was over twofold higher when administered via i.p. than via p.o. administration. The newly obtained information from our study will provide important reference for dauricine dose and administration route in designing dauricine therapy for applicable diseases.
[1]. M.C. Li D.Y. Huang 2008 Chin. Pharm. J. 43 1875–1877.
[2]. Z.K. Huang 2004 Modern Journal of Integrated Traditional Chinese and Western Medicine 13 718–719.
[3]. Q.Y. Li J.Y. Wang J.J. Cheng 2010 Progress in Veterinary Medicine 31 115–117.
[4]. Pharmacopoeia Commission of People's Republic of China. Pharmacopoeia of People's Republic of China, 1st edn. Chemical Industry Press, Beijing, 2005.
[5]. Y. Zhang C. Sun Q.C. Guan et al.2009 Modern Pharmacy and Clinic 24 367–368.
[6]. M. Li B.E. Shan 2005 International Journal of Traditional Chinese Medicine 27 267–271.
[7]. X.Q. Zhu T.G. Han 2007 Journal of Chengde Medical College 24 418–420.
[8]. X.D. Huang D. Han X.Y. Cui 2007 Medical Journal of Chinese People's Health 19 575–576.
[9]. J.Q. Qian 2002 Acta Pharmacol Sin 23 1086–1092.
[10]. H. Tian Q.C. Pan 1996 Cancer 15 410–414.
[11]. J.H. Li F.Q. Qin P.M. Yang 2002 Journal of Dalian Medical University 24 94–96.
[12]. L. He G.Q. Liu 2002 Acta Pharmacol Sin 23 591–596.
[13]. F.M. Han Z.H. Peng W. Song et al.2007 Journal of Chromatography B 854 1–7.
[14]. X.Y. Liu Q. Liu D.M. Wang et al.2010 Journal of Chromatography B 878 1199–1203.
[15]. S.J. Chen B. Zhang Y.M. Yang Z.S. Dai et al.2000 Chinese Journal Of Clinical Pharmacology and Therapeutics 5 213–217.
[16]. S.J. Chen Y.M. Yang 2001 Chinese Pharmacological Bulletin 17 225–229.
[17]. R. Sun C. Wang 2009 Chinese Journal of Pharmacovigilance 6 546–549.
[18]. V.J. Wacher L. Salphati L.Z. Benet 2001 Advanced Drug Delivery Reviews 46 89–102.