Determination of HP 749, a potential therapeutic agent for Alzheimer's disease, in plasma by high-performance liquid chromatography.
N-(n-Propyl)-N-(4-pyridinyl)-1H-indol-1-amine hydrochloride (HP 749, I), a non-receptor-dependent cholinomimetic agent with noradrenergic activity, is a potential agent for the treatment of Alzheimer's disease. Pharmacokinetic studies in animals and humans showed that I was well absorbed and metabolized primarily to the N-despropyl metabolite (P7480, II) after oral administration. To facilitate the kinetic studies, a sensitive and selective high-performance chromatographic assay was developed. I and II are extracted from plasma by a mixture of cyclohexane-ethyl acetate and chromatographed on an isocratic reversed-phase high-performance liquid chromatographic system employing an analytical phenyl column with acetonitrile-ammonium formate as mobile phase. The concentrations of these two compounds, quantitated by internal standardization, are monitored by ultraviolet detection. The method is linear in the plasma assay over a concentration range of 0.5-500 ng/ml for both compounds with a quantitation limit of 0.5 ng/ml. The precision and accuracy of the calibration curves and/or method are less than 10%. The recovery of I and II from plasma is 63-74 and 63-68%, respectively, over a concentration range of 0.5-500 ng/ml.
Hsu
R S
RS
Chemical Research Department, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ 08876.
DiLeo
E M
EM
Chesson
S M
SM
Klein
J T
JT
Effland
R C
RC
D000544:Alzheimer Disease / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D011725:Pyridines / Q000097:blood* / Q000627:therapeutic use; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
D007211:Indoles; D011725:Pyridines; C074872:besipirdine