Micellar electrokinetic capillary chromatography (MECC) is shown to be a quantitative method for the determination of theophylline in capillary ultrafiltrates of biological systems. MECC exhibits reproducibility in migration times of 1.3% relative standard deviation (R.S.D.) (n = 31) and peak heights of 3.0% R.S.D. (n = 28). MECC and reversed-phase liquid chromatography (LC) are shown to be complementary techniques for the determination of theophylline in ultrafiltrate samples. In vivo sampling of awake, freely moving rats is achieved using capillary ultrafiltration probes implanted in subcutaneous tissue. The ability of MECC coupled with in vivo capillary ultrafiltration to determine theophylline pharmacokinetics is demonstrated. The half-life of elimination for a 15 mg/kg intraperitoneal dose of theophylline was determined to be 3.1 +/- 0.4 h for MECC and 3.2 +/- 0.4 h for LC (n = 4, mean +/- standard error of the mean). Concurrent results for derived pharmacokinetic parameters (area under the curve, volume of distribution, concentration at time zero and clearance) were obtained for MECC and LC.
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