Hsu R S, DiLeo E M, Chesson S M, Klein J T, Effland R C
Chemical Research Department, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ 08876.
J Chromatogr. 1991 Dec 6;572(1-2):352-9. doi: 10.1016/0378-4347(91)80503-5.
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.
N-（正丙基）-N-（4-吡啶基）-1H-吲哚-1-胺盐酸盐（HP 749，I）是一种具有去甲肾上腺素能活性的非受体依赖性拟胆碱药，是治疗阿尔茨海默病的潜在药物。在动物和人体进行的药代动力学研究表明，口服给药后，I吸收良好，主要代谢为N-去丙基代谢物（P7480，II）。为便于进行动力学研究，开发了一种灵敏且选择性高的高效色谱分析法。I和II用环己烷-乙酸乙酯混合物从血浆中萃取，并在等度反相高效液相色谱系统上进行色谱分析，该系统采用分析型苯基柱，以乙腈-甲酸铵为流动相。通过内标法定量这两种化合物的浓度，用紫外检测进行监测。该方法在血浆分析中，两种化合物在0.5 - 500 ng/ml浓度范围内呈线性，定量限为0.5 ng/ml。校准曲线和/或方法的精密度和准确度小于10%。在0.5 - 500 ng/ml浓度范围内，I和II从血浆中的回收率分别为63 - 74%和63 - 68%。
