Permeability of atenolol and propranolol in the presence of dimethyl sulfoxide in rat single‐pass intestinal perfusion assay with liquid chromatography/UV detection

Abstract

A simple and sensitive RP-HPLC-UV method was developed and validated for simultaneous determination of atenolol and propranolol and subsequently applied to investigate the effect of dimethyl sulfoxide in rat in situ intestinal permeability studies. Atenolol (400 microm) and propranolol (100 microm) were perfused in the small intestine of anaesthetized (pentobarbitone sodium 60 mg/kg, i.p.) male Sprague-Dawley rats either in the presence (1, 3 and 5%) or in the absence of dimethyl sulfoxide. There was no significant alteration (p > 0.05) in the permeability of atenolol and propranolol, which indicated there was no effect of various concentrations of dimethyl sulfoxide (1-5%) on the membrane integrity of the rat intestinal tissues. The analytical method was validated on a C(4) column with a mobile phase comprising ammonium acetate buffer (pH 3.5, 0.02 m) and acetonitrile in the ratio of 30:70 (v/v) at a flow rate of 1.0 mL/min. The validated method was found to be accurate and precise and stability studies were carried out at different storage conditions and both analytes were found to be stable. These findings are applicable for determining the absorbability of water-insoluble drugs and new chemical entities for the purpose of classifying them in the biopharmaceutical classification system.

Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent

“…To determine the reason for the higher exposure of DNJ in rats after administration of SZ–A, the intestinal absorption of the components was investigated through in situ single-pass intestinal perfusion of SZ–A (21.73 μg/mL, containing 50 μM DNJ, 9.5 μM FGM, 7.8 μM DAB) and purified DNJ (50 μM). Here, the P lumen of propranolol and atenolol agreed with previous values obtained in single-pass intestinal perfusion in rats [ 15 ], which suggested that the assay was reliable. The cumulative amount of three alkaloids in mesenteric plasma was increased time–dependently ( Figure 3 ), suggesting that three compounds could be absorbed into blood through the intestinal barrier.…”

Simultaneous determination of nine model compounds in permeability samples using RP-HPLC: Application to prove the cassette administration principle in single pass intestinal perfusion study in rats

“…The P eff values obtained after co-perfusion of markers are in the well agreement in comparison to the permeabilities of the marker compounds perfused alone and the previously reported values [1,4,8,[10][11][12][13][14][15][16][17][18][19][20][21][22]. This indicates that permeability of these compounds is not much affected in the presence of each other.…”

Regional Intestinal Permeability in Rats: A Comparison of Methods

“…Atenolol, metoprolol, ketoprofen, and enalaprilat were added from DMSO stock solutions to the donor chamber medium (mucosal side) to achieve a final concentration of 25 μM for each drug. The final concentration of DMSO never exceeded 0.5% (w/w), which has been validated previously with respect to intestinal tissue integrity …”