Supercritical fluid chromatography with tandem mass spectrometry combined with postcolumn compensation and one‐step acetone protein precipitation to evaluate the bioavailability of probucol solid dispersion tablet

Solid dispersion technology was used to improve the bioavailability of probucol due to its low hydrophilicity and high lipophilicity. In this study, a highly rapid and sensitive supercritical fluid chromatography with tandem mass spectrometry method was optimized and validated for the determination of probucol in beagle dog plasma with diazepam as an internal standard. The analyte and internal standard were extracted by acetone and then separated on a polar 2‐ethylpyridine phase column (100 mm × 3 mm, 1.7 μm) at a flow rate of 1.0 mL/min using CO 2 (≥99.99%) and methanol (95:5, v/v) as the mobile phase. The mass transition ion‐pair was m / z 515.6→236.2 and 285.2→193.1 for probucol and internal standard, respectively. Excellent linearity was observed over the concentration range of 5–5000 ng/mL ( r 2 ≥ 0.9999) with a lower limit of quantification of 5 ng/mL. The intra‐ and inter‐day accuracy and precision for all quality control samples were within ±15%. The proposed method was accurate, rapid and reproducible, which was successfully applied to a bioavailabilty evaluation of probucol solid dispersion tablets.