摘要
为测定血浆中卡托普利及其二硫键代谢物总浓度，以适应临床进行血药浓度监测。用高效液相色谱方法。样品中卡托普利二聚体及卡托普利与氨基酸、血浆蛋白的二硫键结合物采用ＮａＢＨ４还原，释放出卡托普利原形，经液—液提取纯化后，以邻苯二甲醛及Ｄ苯丙氨酸进行衍生化。选用反相ＨＰＬＣ法，荧光检测。此法线性范围为５～３００ｎｇ·ｍｌ－１，最低检测限为５ｎｇ·ｍｌ－１。用本法测定了多名高血压病患者血浆中卡托普利及其二硫键代谢物的总含量。
A new and sensitive HPLC method has been developed for the determination of captopril plus its disulfide metabolites (total captopril) in human plasma. Captopril disulfides and the drug covalently bound to protein were reduced with sodium borohydride to captopril. After liquidliquid extraction, captopril was treated with ophthalaldehyde in the presence of Dphenylalanine. The fluorescent derivative of captopril was measured by HPLC using a C18 reversed phase column with fluorescence detection at the excitation and emission wavelengths of 235 nm and 440 nm, respectively. The mobile phase consisted of a methanolacetonitrilephosphate buffer (0.02 mol·L^(-1), pH 64) mixture (30∶30∶135, v/v), and was set at a flow rate of 1 ml·min^(-1). The linear range of the assay was between 5 ng·ml^(-1) (lower limit of quantitation) and 300 ng·ml^(-1) for total captopril in plasma. The method was successfully applied to determine plasma concentrations of captopril plus its disulfide metabolites in hypertensive patients and was demonstrated to be suitable for the therapeutic drug monitoring.
出处
《药学学报》
CAS
CSCD
北大核心
1998年第8期605-609,共5页
Acta Pharmaceutica Sinica
基金
国家杰出青年科学基金
