Mück W, Bode H
Clinical Pharmacology International, Bayer AG, Wuppertal.
Pharmazie. 1994 Feb-Mar;49(2-3):130-9.
The analytical test procedures currently established for the determination of the dihydropyridine calcium antagonist nimodipine in biological fluids are presented. Method of choice which has been dominantly used in pharmacokinetic investigations and drug interaction studies is gas chromatography with electron-capture detection (GC-ECD) subsequent to simple toluene extraction. The limit of quantification of 0.1 ng/ml in plasma conveniently allows to follow concentration/time profiles in the nano/subnanogram per ml-range after therapeutic doses. If not restricted by its markedly higher limit of quantification of approx. 1-5 ng/ml, high-performance liquid chromatography with either UV- or amperometric detection may be an attractive alternative for therapeutic drug monitoring or compliance control. A combined approach of HPLC and GC--chiral stationary-phase HPLC with GC-MS as off-line detection mode--has proven adequate and efficient to obtain pharmacokinetic data for nimodipine enantiomers after administration of the racemic drug.
本文介绍了目前用于测定生物体液中二氢吡啶类钙拮抗剂尼莫地平的分析测试方法。在药代动力学研究和药物相互作用研究中占主导地位的首选方法是在简单的甲苯萃取后采用电子捕获检测气相色谱法(GC-ECD)。血浆中0.1 ng/ml的定量限便于追踪治疗剂量后每毫升纳克/亚纳克范围内的浓度/时间曲线。如果不受其约1-5 ng/ml明显更高的定量限限制,配备紫外或安培检测的高效液相色谱法可能是治疗药物监测或依从性控制的一个有吸引力的替代方法。一种将高效液相色谱法和气相色谱法相结合的方法——采用手性固定相高效液相色谱法,气相色谱-质谱联用作为离线检测模式——已被证明足以有效地获取外消旋药物给药后尼莫地平对映体的药代动力学数据。