Exploitation of flow-based procedures for reagentless hydrochlorothiazide determination and accelerated degradation studies of pharmaceutical preparations

摘要

Drug quality assessment and stress testing are important to ensure both treatment efficacy and patient safety. High performance liquid chromatography may be considered a standard technique for pharmaceutical analysis, showing good precision and accuracy, but it also involves relatively high cost and low analytical frequency. Flow injection analysis presents high sample throughput, lower cost and might be used for selective drug analysis with an appropriate assay and/or detector. In this paper, for the first time, photoreactions promoted by UV radiation were employed for reagentless spectrophotometric determination of hydrochlorothiazide. Optimized parameters led to a linear range of 50 to 500 mg L-1, estimated limit of detection of 3.0 mg L-1 and 24 determinations per hour. The use of diluted NaOH solution as a carrier allowed solubilization of hydrochlorothiazide and analysis without organic solvents. The presence of the most common excipients was evaluated and no significant interferences were observed. The results from the analysis of samples by the proposed and by the reference procedures demonstrated accuracy and matching results. The proposed in-line photolysis of the pharmaceutical, performed in 5 min, is a promising alternative to the conventional hydrolytic forced degradation, which requires elevated temperature and prolonged time period. To evaluate the degree of photoconversion, a capillary zone electrophoresis method was developed, which performed well for separations manifesting good analytical frequency and reduced amount of waste. The combination of in-line photodegradation followed by separation by capillary electrophoresis is a promising approach for the stress test of hydrochlorothiazide in pharmaceutical formulations.