A Q-TOF LC/MS method for identification and quantitation of Histamine in the antibiotic Gentamicin at ppm level: Validation and uncertainty evaluation

Maria Cristina Gaudiano, Luisa Valvo, Andrea Luca Rodomonte

Research output: Contribution to journalArticlepeer-review

Abstract

Adverse reactions have been reported for antibiotics produced via fermentation with fish peptone due to Histamine contamination. Just few micrograms of Histamine can result in adverse reactions when administered intravenously. Thus in this paper a new method for identification and quantitation of Histamine at ppm levels in the antibiotic Gentamicin is described. The method is based on separation of Histamine from Gentamicin and other excipients present in the drug matrix, by hydrophilic interaction liquid chromatography (HILIC) coupled to a Q-TOF/MS detector; quantitation is based on the standard addition approach. The method was validated for repeatability, inter-day precision, specificity, accuracy (relative and absolute bias) linearity, limit of detection and quantitation. Uncertainty was estimated and evaluated by comparison with values expected according to the Horwitz theory. The method showed satisfactory performances and good sensitivity, reaching a limit of quantitation of approximately 1 ppm. The method proposed can be a starting point for the development of Histamine quantitation methods in other antibiotics or even in other medicinal products which active ingredient is produced via fermentation in presence of fish peptone.

Original languageEnglish
Pages (from-to)158-163
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume162
DOIs
Publication statusPublished - Jan 5 2019

Keywords

  • Anti-Bacterial Agents/analysis
  • Calibration
  • Chromatography, Liquid/standards
  • Drug Contamination
  • Gentamicins/analysis
  • Histamine/adverse effects
  • Reference Standards
  • Reproducibility of Results
  • Tandem Mass Spectrometry/standards
  • Uncertainty

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