Estimation of passive gastrointestinal absorption of selected dual COX-2 and 5-LOX inhibitors using biopartitioning micellar chromatography

Biopartitioning micellar chromatography (BMC) was used to predict passive gastrointestinal absorption of a set of thirteen previously synthesized dual COX-2 and 5-LOX inhibitors. It was performed using ZORBAX Extend-C18 HPLC column (150 mm x 4.6 mm, 5µm). The mobile phase consisted of aqueous phase (40 mmol/l solution of Brij 35 in 7 mmol/l disodium hydrogen phosphate) and acetonitrile (70:30, v/v) and its pH was adjusted to 5.5 by phosphoric acid. The column temperature was set to 36.5 °C, flow rate to 1 ml/min and UV/VIS detection was performed at 240 nm, 254 nm and 400 nm. All tested compounds were injected in duplicates and retention factors (k) were calculated. In addition, effective lipophilicity coefficients (logD) were predicted at pH 5.5 using MarvinSketch 21.4. Retention factors ranged from 0.92 to 36.96. Compound 9 had the lowest k value (0.92), so the lowest passive gastrointestinal absorption can be expected. Low lipophilicity of this compound (logD = - 0.21) is due to the presence of carboxylic acid group, which is ionized at pH 5.5. The most lipophilic compound (13, logD = 5.21) had the highest k value (36.96), so the highest passive gastrointestinal absorption can be expected. The most promising dual COX-2 and 5-LOX inhibitors (1, 2 and 3) had intermediate k and logD values (k: 9.50, 5.55 and 9.33; logD: 2.15, 2.75 and 2.80, respectively). The applied BMC model highlighted compounds with the highest and lowest expected passive gastrointestinal absorption. Obtained results also proved the influence of lipophilicity on BMC retention.