Dru J D, Hsieh J Y, Matuszewski B K, Dobrinska M R
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
J Chromatogr B Biomed Appl. 1995 Apr 21;666(2):259-67. doi: 10.1016/0378-4347(94)00579-t.
Sensitive methods based on capillary gas chromatography (GC) with mass spectrometric (MS) detection in a selected-ion monitoring mode (SIM) for the determination of racemic felodipine, its enantiomers, and a pyridine metabolite in human plasma are described. Following liquid-liquid extraction from plasma, enantiomers of felodipine were separated on a chiral HPLC column (Chiralcel OJ) and fractions containing each isomer were collected on a continuous basis using a fraction collector. These fractions were later analyzed by GC-MS-SIM. A similar method based on GC-MS-SIM detection was developed for the determination of racemic felodipine and its pyridine metabolite with a minor modification of sample preparation. The limits of quantitation in plasma were 0.1 ng/ml for both the R(+)- and S(-)-enantiomers of felodipine and 0.5 ng/ml for both racemic felodipine and its pyridine metabolite. The stereoselective assay was used to support a clinical study with racemic felodipine, and was capable of analyzing more than 30 plasma samples per day.
本文描述了一种灵敏的方法，该方法基于毛细管气相色谱（GC）与质谱（MS）检测，采用选择离子监测模式（SIM），用于测定人血浆中的外消旋非洛地平、其对映体以及一种吡啶代谢物。从血浆中进行液-液萃取后，非洛地平的对映体在手性高效液相色谱柱（Chiralcel OJ）上分离，并使用馏分收集器连续收集含有每种异构体的馏分。这些馏分随后通过GC-MS-SIM进行分析。基于GC-MS-SIM检测开发了一种类似的方法，用于测定外消旋非洛地平及其吡啶代谢物，只是在样品制备上有微小改动。血浆中R(+)-和S(-)-非洛地平对映体的定量限均为0.1 ng/ml，外消旋非洛地平及其吡啶代谢物的定量限均为0.5 ng/ml。该立体选择性测定法用于支持一项关于外消旋非洛地平的临床研究，并且每天能够分析超过30份血浆样品。
