A HPLC method for determination of nicousamide in dog plasma and its application to pharmacokinetic studies.
A sensitive and reproducible high performance liquid chromatography (HPLC)-UV method for determination of nicousamide, an inhibitor of rennin and transforming growth factor-beta1 (TGF-beta1) type II receptors, has been developed and validated. Following acetonitrile deproteiniation, samples were separated by isocratic reversed-phase HPLC on an Aichrom Bond-AQ C(18) column and quantified using UV detection at 320 nm. The mobile phase was acetonitrile/water (ratio 62:38 containing 0.1% H(3)PO(4)), with a flow-rate of 1.0 ml/min. A linear curve over the concentration range 5-200 ng/ml (r(2)=0.9978) was obtained. The coefficients of the variation for the intra- and inter-day precisions ranged from 1.4-10.7% and 1.8-7.1%, respectively. The percentage of relative recovery was 91.56-105.45%. The method was used to determine the plasma concentration-time profiles for nicousamide after oral doses of 30, 100 and 300 mg/kg in dogs. A nonlinear pharmacokinetics was found in dogs at doses from 30 to 300 mg/kg. Following 30 mg/kg oral dose, the C(max) and AUC in females were lower than that in male. There is a potential for accumulation in dogs following multiple doses.
Sheng
Li
L
Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China. shengli@imm.ac.cn
Chen
Hui
H
Li
Yan
Y
D000814:Aniline Compounds / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003374:Coumarins / Q000097:blood* / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D008297:Male; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
D000814:Aniline Compounds; D003374:Coumarins; C523324:nicousamide