A General LC-MS/MS Method for Monitoring Potential β-Lactam Contamination in Drugs and Drug-Manufacturing Surfaces
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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 WORDScross contamination LC-MS/MS parallel reaction monitoring penicillin β-lactams
- 1.Rossi S. In: Rossi S, editor. Australian medicines handbook. AMH Pty Ltd: Adelaide; 2006.Google Scholar
- 15.FDA guidance for industry. Available from: https://www.fda.gov/downloads/Drugs/Guidances/UCM246958.pdf.
- 16.Carter GG. A review of procedures for the detection of residual penicillins in drugs. FDA By-Lines. 1977;8:119–37.Google Scholar
- 21.Fedorava G, Nebesky V, Randak T, Grabic R. Simultaneous determination of 32 antibiotics in aquaculture products using LC-MS/MS. Chem Pap. 2014;68(1):29–36.Google Scholar
- 27.Yao J, Moellering R. Antibacterial agents. In: Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D, editors. Manual of clinical microbiology. 10th ed. Washington, DC: American Society for Microbiology; 2011. p. 1043–81.Google Scholar