Chromatography of calcium channel blockers.

Numerous publications during the past ten years have described the determination of various calcium channel blockers in biological fluids, using gas and liquid chromatographic techniques. Diltiazem, verapamil, flunarizine and a growing number of dihydropyridines belong to this group of drugs, which in most instances are active at low plasma concentrations. From a bioanalytical point of view these compounds have many features in common, such as high lipophilicity and favourable detection properties.

Comparison of high-selectivity gas chromatographic methods, including column switching, for the determination of felodipine in plasma.

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.

Drug level monitoring: cardiovascular drugs.

Methods for the determination of cardiovascular drugs in blood and plasma are critically reviewed with emphasis on gas and liquid chromatographic techniques. The importance of the various procedures is discussed, in particular sample work-up where the conditions for isolation and derivatization of the compounds are decisive for the accuracy and precision of the methods. Compared with other assay techniques chromatographic methods are generally to be preferred owing to their better selectivity. In the review the following groups are discussed: digitalis glycosides, antiarrhythmic agents, beta-adrenoceptor antagonists, vasodilating agents, antihypertensive compounds, and diuretics.

Determination of felodipine in plasma by capillary gas chromatography with electron capture detection.

Felodipine in plasma was extracted with toluene and determined by automated capillary gas chromatography with electron capture detection. Undesirable oxidation of the dihydropyridine derivative in the injector and in the column was avoided by the use of glass materials with the inner surfaces treated by high-temperature silylation. The day-to-day reproducibility of the method was represented by a relative standard deviation (RSD) of 5% for a felodipine concentration of 25 nmol/l. The minimum determinable concentration (giving better than 15% RSD) was 1-2 nmol/l (0.4-0.8 ng/ml).