[Determination of guanfu base A hydrochloride in plasma by LC-MS method and its pharmacokinetics in dogs].
OBJECTIVE
To establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs.


METHODS
Six dogs were given a 7.56 mg.kg-1 dose intravenously. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry (LC-MS) was established to determine the plasma concentration of GFA. Pharmacokinetic evaluation was carried out using the 3P87 program.


RESULTS
The calibration curves were linear over the concentration range from 0.42 microgram.mL-1 to 21.2 micrograms.mL-1 (gamma = 0.9994). The intra-day and inter-day precisions were generally good (< 15%) at low, medium and high concentrations. The overall recovery of the analytes was more than 80%. Six dogs were given an i.v. dose of 7.56 mg.kg-1 of GFA hydrochloride, an open three compartment model best described the concentration-time profiles for GFA. The half-lives for the rapid and slow distribution phase and terminal elimination phase (T1/2 pi, T1/2 alpha and T1/2 beta) were 0.07 h, 1.5 h, and 13.5 h, respectively. The total area under the plasma concentration-time curve (AUC), the volume of the central compartment (Vc), and plasma clearance (CLs) were 61.43 micrograms.h.mL-1, 0.37 L.kg-1 and 0.14 L.kg-1.h-1, respectively.


CONCLUSIONS
The analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.
Wu
Min-shu
MS
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Wang
Guang-ji
GJ
Cai
Xiao-hui
XH
Sun
Jian-guo
JG
Liu
Jing-han
JH
D031841:Aconitum / Q000737:chemistry; D000470:Alkaloids / Q000097:blood* / Q000302:isolation & purification / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods; D004285:Dogs; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006576:Heterocyclic Compounds, 4 or More Rings; D008297:Male; D008657:Metabolic Clearance Rate; D010946:Plants, Medicinal / Q000737:chemistry
D000470:Alkaloids; D006576:Heterocyclic Compounds, 4 or More Rings; C040615:Guan-fu base A