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The AAPS Journal

, 20:70 | Cite as

A General LC-MS/MS Method for Monitoring Potential β-Lactam Contamination in Drugs and Drug-Manufacturing Surfaces

  • Chen Qiu
  • Hongbin Zhu
  • Connie Ruzicka
  • David Keire
  • Hongping Ye
Research Article
  • 182 Downloads

Abstract

Penicillins and some non-penicillin β-lactams may cause potentially life-threatening allergic reactions. Thus, possible cross contamination of β-lactams in food or drugs can put people at risk. Therefore, when there is a reasonable possibility that a non-penicillin product could be contaminated by penicillin, the drug products are tested for penicillin contamination. Here, a sensitive and rapid method for simultaneous determination of multiple β-lactam antibiotics using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated. Mass spectral acquisition was performed on a Q-Exactive HF mass spectrometer in positive ion mode with parallel reaction monitoring (PRM). The method was validated for seven β-lactam antibiotics including one or two from each class and a synthetic intermediate. The quantification precision and accuracy at 200 ppb were in the range of ± 1.84 to ± 4.56 and − 5.20 to 3.44%, respectively. The limit of detection (LOD) was 0.2 ppb, and the limit of quantitation (LOQ) was 2 ppb with a linear dynamic range (LDR) of 2–2000 ppb for all eight β-lactams. From various drug products, the recoveries of eight β-lactams at 200 and 2 ppb ranged from 93.8 ± 3.2 to 112.1 ± 4.2% and 89.7 ± 4.6 to 110.6 ± 1.9%, respectively. The application of the method for detecting cross contamination of trace β-lactams (0.2 ppb) and for monitoring facility surface cleaning was also investigated. This sensitive and fast method was fit-for-purpose for detecting and quantifying trace amount of β-lactam contamination, monitoring cross contamination in manufacturing processes, and determining potency for regulatory purposes and for quality control.

KEY WORDS

cross contamination LC-MS/MS parallel reaction monitoring penicillin β-lactams 

Notes

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Chen Qiu
    • 1
  • Hongbin Zhu
    • 1
    • 2
  • Connie Ruzicka
    • 1
  • David Keire
    • 1
  • Hongping Ye
    • 1
  1. 1.Division of Pharmaceutical Analysis, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSt. LouisUSA
  2. 2.ThermoFisher Scientific Inc.RockfordUSA

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