Graf P, Frueh F, Schmid K
Research and Development Department, CIBA-GEIGY Limited, Basle, Switzerland.
J Chromatogr. 1988 Mar 18;425(2):353-61. doi: 10.1016/0378-4347(88)80039-2.
An enzyme inhibition assay for the angiotensin-converting enzyme (ACE) inhibitor benazeprilat is described. Plasma and urine samples were diluted and endogenous ACE was inactivated by heating. After incubation of the plasma samples with hippuryl-histidyl-leucine as substrate and blank plasma as the source of ACE, released hippuric acid was measured by high-performance liquid chromatography. Urine samples were incubated with [3H] hippuryl-glycyl-glycine and with rabbit lung extract as the source of ACE. Released [3H] hippuric acid was quantified by liquid scintillation counting. Drug standards for the standard curve were prepared in the biological matrix. A cross-check with a gas chromatographic-mass spectrometric method showed good agreement, demonstrating that this enzymic method is suitable for assessing drug bioavailability and pharmacokinetics.
描述了一种用于血管紧张素转换酶(ACE)抑制剂贝那普利拉的酶抑制测定法。血浆和尿液样本经稀释,内源性ACE通过加热使其失活。将血浆样本与马尿酰-组氨酰-亮氨酸作为底物以及空白血浆作为ACE来源一起孵育后,通过高效液相色谱法测量释放的马尿酸。尿液样本与[3H]马尿酰-甘氨酰-甘氨酸以及兔肺提取物作为ACE来源一起孵育。通过液体闪烁计数法定量释放的[3H]马尿酸。标准曲线的药物标准品在生物基质中制备。与气相色谱-质谱法的交叉核对显示出良好的一致性,表明这种酶法适用于评估药物的生物利用度和药代动力学。