Bonke Gitte, Jensen Berit P
Clinical Pharmacology, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand.
Bioanalysis. 2010 Sep;2(9):1553-60. doi: 10.4155/bio.10.89.
A fast and sensitive validated assay for nortriptyline, E-10-hydroxynortriptyline and Z-10-hydroxynortriptyline in plasma following a single oral dose of nortriptyline 25 mg was needed to support a clinical study.
Plasma samples were prepared by protein precipitation, separated on a C18 column with a mobile phase consisting of 0.1% formic acid in an acetonitrile gradient over 6 min and detected by ESI in the positive mode and MS/MS. Mean recoveries of at least 90% were achieved. The LLOQ was 0.2 ng/ml for nortriptyline and 0.5 ng/ml for the metabolites. The standard curve was linear within LLOQ to 40 ng/ml (r(2) ≥ 0.997), precision was under 7.1% coefficient of variance (<16% at LLOQ) and accuracy was 92-114%.
A fast and sensitive assay for nortriptyline, E- and Z-10-hydroxynortriptyline in plasma was developed and validated. It has been applied successfully to a clinical study.
为支持一项临床研究，需要一种快速、灵敏且经过验证的方法来测定单次口服25毫克去甲替林后血浆中的去甲替林、E-10-羟基去甲替林和Z-10-羟基去甲替林。
血浆样本通过蛋白沉淀法制备，在C18柱上分离，流动相为含0.1%甲酸的乙腈梯度溶液，6分钟内完成分离，采用电喷雾电离正离子模式和串联质谱进行检测。平均回收率至少达到90%。去甲替林的定量下限为0.2纳克/毫升，代谢物的定量下限为0.5纳克/毫升。标准曲线在定量下限至40纳克/毫升范围内呈线性（r(2)≥0.997），精密度变异系数低于7.1%（定量下限处<16%），准确度为92-114%。
已开发并验证了一种快速、灵敏的血浆中去甲替林、E-10-羟基去甲替林和Z-10-羟基去甲替林的检测方法。该方法已成功应用于一项临床研究。
