Franklin M E, Addison R S, Baker P V, Hooper W D
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Australia.
J Chromatogr B Biomed Sci Appl. 1998 Jan 23;705(1):47-54. doi: 10.1016/s0378-4347(97)00481-7.
An enhanced, sensitive GC-MS assay is presented for the highly specific angiotensin-converting enzyme (ACE) inhibitor, captopril. This method improves previously published assays by using solid NEM as stabilizer in the collection tubes, a rapid extraction technique with dichloromethane and back-extraction into base, a commercially available internal standard (thiosalicylic acid) and a capillary GC column. Captopril and the internal standard are measured as their bis-pentafluorobenzyl derivatives. The assay was linear from 10 to 5000 ng/ml with a mean recovery following solvent extraction at 50, 200 and 1000 ng/ml of 77%. At mean values of 45.9, 187 and 980 ng/ml inter-assay precision and accuracy were 4.0, 2.9 and 3.5% and 8.2, 6.5 and 3.1%, respectively. Analysis of captopril concentrations in plasma samples from 20 volunteers following oral administration of 100 mg of captopril provided the following pharmacokinetic data (mean+/-S.D.): Cmax, 1470+/-467 ng/ml; AUC(0-infinity), 1736+/-481 ng/ml.h; Tmax, 0.73 h; k(e), 0.468+/-0.122 h(-1); elimination half life, 1.58/-0.41 h.
本文介绍了一种用于高特异性血管紧张素转换酶（ACE）抑制剂卡托普利的增强型灵敏气相色谱-质谱（GC-MS）测定法。该方法通过在收集管中使用固体N-乙基马来酰亚胺（NEM）作为稳定剂、采用二氯甲烷快速萃取技术并反萃取至碱液、使用市售内标（硫代水杨酸）以及毛细管气相色谱柱，改进了先前发表的测定法。卡托普利和内标以其双五氟苄基衍生物的形式进行测定。该测定法在10至5000 ng/ml范围内呈线性，在50、200和1000 ng/ml进行溶剂萃取后的平均回收率为77%。在45.9、187和980 ng/ml的平均值下，批间精密度和准确度分别为4.0%、2.9%和3.5%以及8.2%、6.5%和3.1%。对20名志愿者口服100 mg卡托普利后血浆样品中卡托普利浓度的分析提供了以下药代动力学数据（平均值±标准差）：Cmax，1470±467 ng/ml；AUC(0-∞)，1736±481 ng/ml·h；Tmax，0.73 h；k(e)，0.468±0.122 h-1；消除半衰期，1.58±0.41 h。
