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

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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.

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Author notes

  1. Hongbin Zhu

    Present address: ThermoFisher Scientific Inc., 3747 N Meridian Rd, Rockford, Illinois, 61101, USA

Authors and Affiliations

  1. Division of Pharmaceutical Analysis, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 645 S. Newstead Ave, St. Louis, Missouri, 63110, USA

    Chen Qiu, Hongbin Zhu, Connie Ruzicka, David Keire & Hongping Ye

Authors
  1. Chen Qiu
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  2. Hongbin Zhu
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  3. Connie Ruzicka
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  4. David Keire
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  5. Hongping Ye
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Correspondence to Hongping Ye.

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This publication reflects the views of the authors and should not be construed to represent the FDA’s views or policies.

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Qiu, C., Zhu, H., Ruzicka, C. et al. A General LC-MS/MS Method for Monitoring Potential β-Lactam Contamination in Drugs and Drug-Manufacturing Surfaces. AAPS J 20, 70 (2018). https://doi.org/10.1208/s12248-018-0224-7

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  • DOI: https://doi.org/10.1208/s12248-018-0224-7

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