The Human Pharmacokenetic Study And Content Determination Study Of Ibuprofen And Pseudoephedrine Soft Capsules

Two specific,sensitive and simple HPLC-UV methods were developed to determine ibuprofen and pseudoephedrine hydrochloride levels in human plasma. The methods were successfully used in pharmacokinetic study of ibuprofen and pseudoephedrine soft capsules. And study on the method for determination of ibuprofen and pseudoephedrine hydrochloride in ibuprofen and pseudoephedrine soft capsules.1. The method for determination of ibuprofen in human plasmaIbuprofen and the internal standard, indomethacin were separated on a Diamonsil C₁₈ column after protein precipitation with acetonitrile. The mobile phase was methanol - 0.02mol/L sodium dihydrogen phosphate(pH 3.3)(77:23,v/v). The flow rate was set at 1.0mL/min. The UV detector was set at 225 nm. The linear calibration curve was obtained in the concentration range of 0.220-264μg/mL. The lower limit of quantification (LLOQ) was 0.220μg/mL. The intra-day and inter-day precisions, expressed as the relative standard deviation (RSD), were less than 9.9% and10.2%. The accuracy was within±7.1% in terms of relative error.2. The method for determination of pseudoephedrine hydrochloride in human plasmaThe analytes were extracted from alkaline plasma samples with hexane - ether (1:1,v/v). The pseudoephedrine hydrochloride and the internal standard, matrine hydrochloride were separated on a Diamonsil C18 column. The mobile phase was methanol - 0.02mol/L sodium dihydrogen phosphate and 0.005mol/L sodium 1-octanesulfonate (pH 3.8)(45:55,v/v). The flow rate was set at 0.7mL/min. The UV detector was set at 210 nm. The linear calibration curve was obtained in the concentration range of 10⁷50ng/mL. The lower limit of quantification (LLOQ) was 10ng/mL. The intra-day and inter-day precisions, expressed as the relative standard deviation (RSD) , were less than 10.8% and 13.3%, determined from QC samples for pseudoephedrine hydrochloride. Theaccuracy was within±1.4% in terms of relative error.3. The Pharmacokinetics of ibuprofen and pseudoephedrine soft capsuleThe ibuprofen and pseudoephedrine soft capsules(T) and compound ibuprofen tablets(R) of single dose were orally administrated to heathy Chinese male volunteers in randomized crossover design. The plasma concentrations of ibuprofen and pseudoephedrine hydrochloride in human plasma were determined and the main Pharmacokinetics parameters were calculated. Results: On the plasma-concentration - time curves of test product and controlled product , ibuprofen and pseudoephedrine hydrochloride were fitted to the one compartment opened model with first - order absorption. The data of AUC and Cmax were log-transformed before analysis of variance(ANVOA), two sides t-test justified bioequivalence. The statistical results showed two products had bioequivalence in vivo. The relative bioavailability of ibuprofen and pseudoephedrine hydrochloride was found to be 107.8±8.3% and 99.5±5.4% respectively.4. The determination of ibuprofen and pseudoephedrine in soft capsulesA reversed-phase paired ion chromatography and exstandard method for the simultaneous determination of ibuprofen and pseudoephedrine hydrochloride in soft capsules was developed. The two components were assayed on DiamonsilTM column with a mobile phase composed of acetonitrile - 0.005 mol/L sodium 1-octanesulfonate - glacial acetic acid (55:45:0.1,v/v/v) at a flow rate 1.0mL/min, The column temptemperature was 40℃. The detection wavelength was 210 nm. The linear rangesof ibuprofen and pseudoephedrine hydrochloride were within 50-500μg/mL(r=0.9996), 7.5-75μg/mL (r=0.9995) respectively.