Automated stopped-flow system in pharmaceutical and clinical analysis

Abstract

Abstract The development of automated stopped-flow spectrophotometric systems, their potential in automated routine determinations using kinetic and fast equilibrium techniques and several examples of applications are briefly reviewed. The use of a compact, inexpensive laboratory-made stopped-flow system for the measurement of reaction rates and a fast equilibrium method for the determination of acetaminophen in formulations and serum are described. The reaction-rate method is based on monitoring the oxidation of acetaminophen by iron(III) in the presence of the chelating agent 2,4,6-tris(2-pyridyl)-s-triazine to form a highly absorbing complex of iron(II). The calibration graph is linear in the range 20–200 μg ml−1, with a precision of 0.8–2.6%, a detection limit of 5.5 μg ml−1 and a measurement throughput of 120 per hour. Common excipients do not interfere and the analysis of commercial formulations gave results similar to those of a reference method. The optimization of the experimental conditions was done by a kinetic study of the reaction and some kinetic parameters are given. The method for the determination of acetaminophen in serum is based on a rapid measurement of the absorbance of the reaction mixture after a delay time of 15 s in the presence of chlorpromazine, which catalyses the reaction. Acetaminophen is isolated by extraction with ethyl acetate and the calibration graph is linear in the range 0.5–6 μg ml−1 with a detection limit of 0.04 μg ml−1 and a precision of 1.5%. The proposed method showed a decreased interference from drugs that also react with iron(III).