Application of advanced high resolution mass spectrometric techniques for the analysis of losartan potassium regarding known and unknown impurities.

Autor: Backer L; University of Würzburg, Institute for Pharmacy and Food Chemistry, 97074 Würzburg, Germany., Buschmann H; RD&C Research, Development & Consulting GmbH, 1170 Vienna, Austria., Kinzig M; IBMP - Institute for Biomedical and Pharmaceutical Research, 90562 Nürnberg-Heroldsberg, Germany., Sörgel F; IBMP - Institute for Biomedical and Pharmaceutical Research, 90562 Nürnberg-Heroldsberg, Germany., Scherf-Clavel O; Ludwig-Maximilians-Universität München, Department of Pharmacy, 81377 Munich, Germany. Electronic address: oliver.scherf-clavel@cup.lmu.de., Holzgrabe U; University of Würzburg, Institute for Pharmacy and Food Chemistry, 97074 Würzburg, Germany. Electronic address: ulrike.holzgrabe@uni-wuerzburg.de.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Mar 15; Vol. 240, pp. 115955. Date of Electronic Publication: 2024 Jan 04.
DOI: 10.1016/j.jpba.2023.115955
Abstrakt: Recalls of medicinal products can cause supply bottlenecks. This is often due to the findings of unexpected impurities that pose a health risk to patients. A recent example is losartan potassium which was contaminated with azido-impurities. The choice of the analytical method determines which substances can be detected and thus controlled. In this study a combination of an untargeted screening approach for impurities and a targeted evaluation of high-resolution mass spectrometry data was applied to search for impurities not described so far, leaving out a precise quantification. Six losartan potassium samples were studied regarding known and unknown impurities and hence highlight the applicability and capability of the approach. For separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and an electrospray ionization in positive and negative mode for mass spectrometric detection was used. An information-dependent acquisition method was applied for the measurement of losartan potassium samples. The untargeted data evaluation using general unknown comparative screening revealed the presence of N-methyl-2-pyrrolidone (NMP) and another impurity from synthesis. The identity of NMP was corroborated by a spiking experiment and the amount was estimated by means of standard addition. A targeted data evaluation by generating extracted ion chromatograms resulted in finding of four additional impurities. Combined approaches like this are needed to detect and respond to changes in the quality of drugs precociously.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura Backer reports financial support was provided by Frankfurt Foundation Quality of Medicines. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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