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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (6): 674-680.doi: 10.3736/jcim20120612

• Original Experimental Research • Previous Articles     Next Articles

A comparison study of pharmacokinetics between bufalin-loaded bovine serum albumin nanoparticles and bufalin in rats

Hui-qing Zhang1,2, Zi-fei Yin2, Jia-yu Sheng1,2, Zhu-qian Jiang1,2, Bao-yu Wu1,2, Yong-hua Su2()   

  1. 1. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
  • Received:2012-03-22 Accepted:2012-04-10 Online:2012-06-20 Published:2018-06-15
  • Contact: Su Yong-hua E-mail:suyh2001@126.com

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Objective: To determine the bufalin concentration in rats’ plasma by establishing a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and to evaluate and compare the pharmacokinetic characteristics of bufalin-loaded bovine serum albumin nanoparticles (bufalin-BSA-NP) and bufalin.
Methods: Thirty Wistar rats were randomly divided into six groups with five rats in each group, and administered with a single dose of 0.6, 0.3 and 0.15 mg/kg of bufalin-BSA-NP or bufalin, respectively. After the administration, blood samples were collected from the orbital venous plexus at designed time points (1, 5, 8, 10, 15, 20, 30, 45, 60, 120, 180, 300 and 480 min). The concentration of bufalin in plasma at different sampling time points was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and compared.
Results: The established HPLC-MS/MS method had high linearity, precision and accuracy. The blood plasma area under curve, the mean retention time and the terminal half life of bufalin-BSA-NP were 1.19 to 1.81, 2.12 to 3.61 and 2.17 to 2.94 times of bufalin, respectively.
Conclusion: Bufalin-BSA-NP has the function of sustained release thus to prolong the bufalin remaining in blood.

Key words: bufalin, nanoparticles, pharmacokinetics, chromatography, high-pressure liquid, tandem mass spectrometry, rats

Figure 1

Chemical structure of bufalin (A) and cinobufagin (B)"

Figure 2

Product irons of bufalin (A) and cinobufagin （B, internal standard）"

Figure 3

HPLC-MS/MS chromatograms of bufalin A: a blank plasma; B: a blank plasma sample spiked with bufalin and IS; C: plasma sample collected from a rat 15 min after intravenous administration of bufalin at a dose of 0.3 mg/kg. IS: internal standard; MRM: multiple reactions monitoring; HPLC-MS/MS: high-performance liquid chromatography-tandem mass spectrometry."

Figure 4

Mean plasma concentration-time curve of bufalin in rats after a single dose of 0.6 (A), 0.3 (B) or 0.15 mg/kg (C) Data are represented as mean±standard division, n=5. Bufalin-BSA-NP: bufalin-loaded bovin serum albumin nanoparticle."

Table 1

Pharmacokinetic parameters of bufalin and bufalin-BSA-NP in rats after a single dose of 0.6, 0.3 or 0.15 mg/kg"

Group Dose
(mg/kg)		 Cmax
(ng/mL)		 t1/2
(min)		 MRT
(min)		 AUC0~8
(ng·h/mL)		 AUC0~∞
(ng·h/mL)		 Vd
(L/kg)		 CL
(L/(h·kg))
Bufalin 0.6 2 430.5 43.2 19.2 299.7 302.60 0.64 2.00
0.3 682.3 39.0 24.6 126.6 128.22 0.95 2.34
0.15 515.6 34.8 24.0 77.6 78.53 0.76 1.93
Bufalin-BSA-NP 0.6 2 186.2 127.2 68.4 380.8 389.70 1.76 1.54
0.3 599.9 93.0 88.8 229.6 233.48 1.90 1.29
0.15 474.3 75.6 51.0 92.5 94.98 1.34 1.58
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