Ultra-performance liquid chromatography-mass spectrometry methods for the determination of the residual quantities of ramipril and hydrochlorothiazide for controlling the cleaning of equipment

Abstract

Monitoring the completeness of equipment cleaning is essential to prevent cross-contamination of medicinal products. Therefore, it is necessary to develop fast and sensitive methods for studying residual quantities of active ingredients on the surfaces of technological equipment. The aim of the work was to develop and validate analytical methods for the determination of ramipril and hydrochlorothiazide in wash waters by ultra-performance liquid chromatography–mass spectrometry method. Materials and methods. In the study, standard samples of ramipril (USP RS) and hydrochlorothiazide (USP RS), as well as class A reagents, were used. Samples were analysed on a liquid chromatograph with an MS detector (Agilent 6420 and Waters Xevo TQD ACQUITY). We used the Kinetex C18 column (2.1 mm × 30 mm × 1.7 μm); mobile phase – 0.1% formic acid solution in deionised water – Acetonitrile (ratio 73:27 for the determination of ramipril and 91.5:8.5 for the determination of hydrochlorothiazide); mobile phase rate of 0.4 mL/min for the determination of ramipril and 0.35 mL/min for the determination of hydrochlorothiazide; column temperature 45 °C for the determination of ramipril and 40 °C for the determination of hydrochlorothiazide, ionisation mode - electric spray in positive mode; The detection parameters are the mode of registration of the daughter ion 417 → 234 m/z for the determination of ramipril and 298 → 281 m/z for the determination of hydrochlorothiazide. Results and discussion. Methods for the determination of ramipril and hydrochlorothiazide in wash waters by ultra-performance liquid chromatography–mass spectrometry have been developed. The developed methods have sufficient linearity, correctness and precision. The sensitivity of the techniques was confirmed at the level of 0.0026 μg/ml. The techniques can be used in the concentration range of 0.0026 – 0.0255 μg/ml Conclusions. Analytical methods for determining ramipril and hydrochlorothiazide in wash waters have been developed and validated.