Details

Autor(en) / Beteiligte

• Szabo, George K.
• J. Pylilo, Richard
• Perchalski, Robert J.
• Browne, Thomas R.

Titel

Simultaneous separation and determination (in serum) of phenytoin and carbamazepine and their deuterated analogues by high-performance liquid chromatography—ultraviolet detection for tracer studies

Ist Teil von

• Journal of Chromatography A, 1990-12, Vol.535 (1-2), p.271-277

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

1990

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• The use of stable isotope-labeled tracer compounds is the safest and most effective method to perform many steady state pharmacokinetic and drug interaction studies. We describe a method by which the heavily deuterated 2H 10 analogues of carbamazepine ( 2H 10 CBZ) and phenytoin ( 2H 10 PHT) can be chromatographically separated by high-performance liquid chromatography from unlabeled CBZ and PHT. All compounds are quantitated against an internal standard (IS) (10,11-dihydrocarbamazepine) and measured using conventional UV detection rather than mass spectrometry. Baseline resolution of extracted serum containing 2H 10 CBZ, CBZ, 2H 10 PHT, PHT and IS is achieved on a heated (55°C) 25 cm × 4.6 mm BioAnalytical Systems Phase II 5 μm ODS column with an isocratic mobile phase consisting of water—acetonitrile—tetrahydrofuran (80:16:4, v/v/v) at 1.2 ml/min. Eluting compounds were monitored at a UV wavelength of 214 nm. Calculated resolution of 2H 10 CBZ from CBZ and of 2H 10 PHT from PHT were 1.3. Serum standard curves were linear ( R ⩾ 0.999) over a range of 0.5–14 μg/ml for 2H 10 CBZ, 0.5–20 μg/ml for CBZ, 0.5–20 μg/ml for 2H 10 PHT, and 0.5–30 μg/ml for PHT. Within-day percent relative standard deviations (precision) were less than 6% in all cases.