Ahnoff M, Ervik M, Johansson L
J Chromatogr. 1987 May 29;394(3):419-27. doi: 10.1016/s0021-9673(01)83809-7.
The selectivity required for the determination of low concentrations of felodipine in plasma was achieved by either mass-selective detection, optimization of stationary phase selectivity or column-switching gas chromatography (GC) with a dual-oven chromatograph, the latter two with electron-capture detection. The three approaches were evaluated in terms of selectivity, detectability, precision and suitability for routine applications with automated injection. Using mass-selective detection, the detectability in plasma samples was limited by the performance of the mass spectrometer. The detection limit (signal-to-noise ratio = 3) was 4.7 pmol (1.8 pg) of felodipine. Pre-concentration of extracts permitted quantitation in plasma down to 0.2 nmol/1. Using electron-capture detection, the detectability was determined by the selectivity and bleeding characteristics of the columns. For single-column separation, a 35% phenyl phase was selected. The detection limit was 3.0 fmol (1.2 pg). The limit of quantitation in plasma was 1 nmol/1. In column-switching GC, bleeding products from the first column will separate on the second column and may interfere in separations for trace analysis. Bleeding products from a 50% phenyl phase (DB-17) were characterised by GC-mass spectrometry. With a dual-column system, employing a DB-17 (50% phenyl) column for selective introduction on to a CP-Sil 5 (0% phenyl) column, the signal-to-noise ratio was limited by the low-bleeding second column, provided that the bleeding products from the first column were adequately separated from felodipine. The detection limit in this instance was significantly lower 0.35 fmol (0.13 pg). Direct injection of plasma extracts permitted quantitation down to 0.4 nmol/l. All three methods were well suited for use with autosamplers.
通过质量选择性检测、固定相选择性优化或使用双柱气相色谱仪的柱切换气相色谱法（GC），可实现血浆中低浓度非洛地平测定所需的选择性，后两种方法采用电子捕获检测。从选择性、可检测性、精密度以及对自动进样常规应用的适用性方面对这三种方法进行了评估。使用质量选择性检测时，血浆样品中的可检测性受质谱仪性能限制。非洛地平的检测限（信噪比 = 3）为4.7皮摩尔（1.8皮克）。提取物的预浓缩可实现血浆中低至0.2纳摩尔/升的定量分析。使用电子捕获检测时，可检测性由色谱柱的选择性和流失特性决定。对于单柱分离，选择了35%苯基固定相。检测限为3.0飞摩尔（1.2皮克）。血浆中的定量限为1纳摩尔/升。在柱切换气相色谱法中，第一根色谱柱的流失产物会在第二根色谱柱上分离，可能会干扰痕量分析的分离。用气相色谱 - 质谱联用仪对50%苯基固定相（DB - 17）的流失产物进行了表征。在双柱系统中，采用DB - 17（50%苯基）色谱柱进行选择性进样到CP - Sil 5（0%苯基）色谱柱上，只要第一根色谱柱的流失产物与非洛地平充分分离，信噪比就受低流失的第二根色谱柱限制。在此情况下，检测限显著降低至0.35飞摩尔（0.13皮克）。直接进样血浆提取物可实现低至0.4纳摩尔/升的定量分析。所有三种方法都非常适合与自动进样器配合使用。
