Sequential Injection Analysis for Pharmaceuticals with Kinetics and Chemometrics Approach

Abstract

Abstract In this study, novel, robust, cost-effective, fully automated methods were provided for the assay of paracetamol,aspirin, promazine hydrochloride and promethazine hydrochloride in pharmaceutical preparations. The newly adopted methods utilized sequential injection analysis (SIA) hyphenated to spectrophotometry with kinetic and chemometric approaches. The methods for the assay of paracetamol and aspirin were based on comprehensive kinetic investigation of the oxidation of the analytes with potassium permanganate in sulphuric acid media. To monitor the reaction kinetics, the absorbance decrease of permanganate was measured at wavelength 526 nm. The newly adopted methods for the assay of paracetamol and aspirin involved full validation by conducting a thorough investigation on the kinetics of the reactions. For paracetamol analysis, the reaction orders with respect to the concentration of the acid, permanganateand paracetamol were found to be inverse one (-1), positive one (+1) and positive one (+1), respectively. The activation energy was examined and the reaction mechanism was postulated. The fixed time kinetic approach was applied for the quantitative determination of the drug. The calibration equation "R = 0.0038C + 0.1209" (R is the response and C is the concentration ofthe analyte in mol l -1 ) with correlation coefficient 0.9931 was found to be linear in the concentration range of 6.61 × 10 -5 - 1.32 × 10 -3 mol l -1 at the fixed time of 70 s at room temperature. The equation was obtained by injecting 35 µl of 1.0 mol l -1 acid, 30 µl of 2.0 × 10 -3 mol l -1 permanganate, 20 µl paracetamol and 25 µl water at the flow rate of 25 µl s -1 . The method was applied for the assay of the drug in tablets and capsules forms. No interference was observed neither from other combined drugs that are diphenylamine hydrochloride, chloroxazone and pseudophedrine hydrochloride nor from excipients. For aspirin analysis, the reaction orderswith respect to the concentration of the acid, permanganate and aspirin werefound to be inverse one (-1), positive one (+1) and positive one (+1), respectively. The activation energy was examined and the reaction mechanism was postulated. The calibration equation "R = -0.09980 + 0.00617C" with correlation coefficient 0.9990 was found to be linear for the drug concentration range between 2.77 × 10 -5 to 2.22 × 10 -3 mol l -1 at a fixed time of 90 s at room temperature.The equation was obtained by injecting 30 µl of 1.0 mol l -1 acid, 30 µl of 2.0×10 -3 mol l -1 permanganate, 20 µl of aspirin and 20 µl of water at flow rate 25 µl s -1 . The method was applied for the determination of aspirin in tablets forms. The results obtained proved to be accurate and precise without suffering from interference of other combined drugs and excipients usually added in tablet formulations. The methods for the assay of phenothiazines were based on their oxidation by cerium(IV) in sulphuric acid media resulting in spectrophotometrically detectable forms measured at wavelength 512 and 514.5 nm for promazine and premethazine, respectively. The methods were chemometrically optimized along with the univariant, ANOVA and multisimplex approaches. The univariant and ANOVA methods were applied for parameters presumed to be potentially affecting the efficiency of the methods, i.e. the acidconcentration, cerium(IV) concentration and flow rate. For the ANOVA approach, a 3 3 factorial design chemometric method was applied. The findings of the main effects and the interaction effects were found to be in agreement with the output of the surface response, which clearly indicate that both the acid concentration and cerium(IV) concentration have greater effect on the response value than the flow rate. It was therefore decided not to incorporate the flowrate as one of the parameters to be optimized in the multisimplex method. In the promazine hydrochloride assay,the optimum operating conditions were found to be 30 µl of 0.004 mol l -1 sulphuric acid, 30 µl of 0.089 mol l -1 cerium(IV) and 30 µl of promazine hydrochloride with a flow rate of 15 µl s -1 . Beer’s law was obeyed in the concentration range of 8.790 × 10 -5 - 5.274 × 10 -4 mol l -1 . In promethazine hydrochloride assay, 30 µl of 0.38 mol l -1 sulphuric acid, 30 µl of 3.99×10 -3 mol l -1 cerium(IV), 20 µl of promethazine hydrochloride and flow rate of 20 µl s -1 were the optimum experimentalconditions. The calibration plot was found to be linear in the concentration range of 7.032 × 10 -5 - 1.563 mol l -1 . The proposed SIA methods were found to be accurate and reproducible when the results were statistically compared with the results obtained by the official BP standard methods. The SIA methods are superior when compared with the official and others non-official standard methods with respect to sample frequency, reagents saving, safety in handling as well to the environment, automation, selectivity and precision and finally accuracy