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A General LC-MS/MS Method for Monitoring Potential β-Lactam Contamination in Drugs and Drug-Manufacturing Surfaces.
- Source :
-
The AAPS journal [AAPS J] 2018 May 15; Vol. 20 (4), pp. 70. Date of Electronic Publication: 2018 May 15. - Publication Year :
- 2018
-
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.
- Subjects :
- Anti-Bacterial Agents chemistry
Chromatography, High Pressure Liquid methods
Drug Compounding instrumentation
Drug Compounding methods
Drug Compounding standards
Equipment Contamination prevention & control
Feasibility Studies
Humans
Limit of Detection
Reproducibility of Results
beta-Lactams chemistry
Anti-Bacterial Agents analysis
Drug Contamination prevention & control
Tandem Mass Spectrometry methods
beta-Lactams analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1550-7416
- Volume :
- 20
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The AAPS journal
- Publication Type :
- Academic Journal
- Accession number :
- 29766324
- Full Text :
- https://doi.org/10.1208/s12248-018-0224-7