Jemal M, Ivashkiv E, Teitz D, Cohen A I
Squibb Institute for Medical Research, Analytical Research and Development Department, New Brunswick, NJ 08903.
J Chromatogr. 1988 Jun 24;428(1):81-92. doi: 10.1016/s0378-4347(00)83892-x.
After oral administration of zofenopril, the active sulfhydryl angiotensin-converting enzyme inhibitor is released. Zofenopril is currently under clinical investigation as an antihypertensive. Blood samples are reacted with N-ethylmaleimide, immediately after collection, processed into plasma and stored frozen for subsequent analysis. After addition of two internal reference standards, one each for the prodrug and the active compound, the plasma samples are purified by a combination of liquid-liquid and solid-phase extractions. The dried methylated extracts are reconstituted with tetramethylbenzene and chromatographed by automated splitless injection on a fused-silica capillary column, connected to a mass-selective detector. The analytes and the internal reference standards are chromatographically resolved and a common fragment ion is monitored for the analytes. A limit of quantitation of approximately 1 ng/ml of plasma is achieved.
口服佐芬普利后，活性巯基血管紧张素转换酶抑制剂被释放出来。佐芬普利目前作为一种抗高血压药物正在进行临床研究。血样采集后立即与N - 乙基马来酰亚胺反应，处理成血浆并冷冻保存以供后续分析。加入两种内标物，分别针对前体药物和活性化合物，血浆样品通过液 - 液萃取和固相萃取相结合的方法进行纯化。干燥的甲基化提取物用四甲苯复溶，并通过自动不分流进样在连接到质量选择检测器的熔融石英毛细管柱上进行色谱分析。分析物和内标物在色谱上得到分离，对分析物监测一个共同的碎片离子。血浆的定量限约为1 ng/ml。
