François-Bouchard M, Simonin G, Boursier-Neyret C
Technologie Servier, Orléans, France.
J Chromatogr B Biomed Sci Appl. 2000 Aug 18;745(2):261-9. doi: 10.1016/s0378-4347(00)00275-9.
A rapid, selective, sensitive and reproducible liquid chromatographic method with tandem mass spectrometric detection has been developed and validated for the analysis of a new specific bradycardic agent, ivabradine (S 16257) and six potentially active metabolites in human plasma. Isolation of these compounds and of the internal standard was performed by an automated solid-phase extraction system using Oasis cartridges. Separation and detection of ivabradine and its metabolites were achieved using a C18 column and a MS-MS detector with a positive electrospray ionization source. Ivabradine and its metabolites gave a linear response ranging from 0.1 or 0.2 to 20 ng/ml and the limits of quantitation ranged from 0.1 to 0.2 ng/ml using a 0.5 ml plasma sample size. A complete validation demonstrated the method to be accurate, precise and specific for the simultaneous quantification of ivabradine and its metabolites in human plasma. The method was subsequently applied to the quantitative determination of ivabradine and its metabolites in human plasma samples from healthy volunteers participating in a clinical study to provide pharmacokinetic data.
已开发并验证了一种采用串联质谱检测的快速、选择性、灵敏且可重现的液相色谱方法，用于分析一种新型特异性心动过缓药物伊伐布雷定（S 16257）及其六种潜在活性代谢物在人血浆中的含量。这些化合物和内标物通过使用Oasis柱的自动固相萃取系统进行分离。伊伐布雷定及其代谢物的分离和检测采用C18柱和带有正电喷雾电离源的MS-MS检测器实现。伊伐布雷定及其代谢物的线性响应范围为0.1或0.2至20 ng/ml，使用0.5 ml血浆样本量时定量限范围为0.1至0.2 ng/ml。完整的验证表明该方法对于同时定量人血浆中的伊伐布雷定及其代谢物准确、精密且具有特异性。该方法随后应用于参与一项临床研究的健康志愿者的人血浆样本中伊伐布雷定及其代谢物的定量测定，以提供药代动力学数据。
