Development and validation of an LC tandem MS assay for the quantification of β-lactam antibiotics in the sputum of cystic fibrosis patients
| Autor: | Leen Van Simaey, Virginie Van Heck, Katrien Forier, Sabine Van daele, Eva Van Braeckel, Alain Verstraete, Frans De Baets, Petra Schelstraete, Filomeen Haerynck, Veronique Stove, Mario Vaneechoutte, Mieke Carlier |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Cystic Fibrosis medicine.drug_class 030106 microbiology Antibiotics Ceftazidime Aztreonam Meropenem 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tandem Mass Spectrometry Tobramycin Medicine Humans Pharmacology (medical) Chromatography High Pressure Liquid Pharmacology Piperacillin Chromatography business.industry Selected reaction monitoring Sputum Anti-Bacterial Agents Infectious Diseases 030228 respiratory system chemistry Thienamycins medicine.symptom business medicine.drug |
| Zdroj: | The Journal of antimicrobial chemotherapy. 73(1) |
| ISSN: | 1460-2091 |
| Popis: | Objectives: Antibiotic therapy is of vital importance for the control of infectious exacerbations in cystic fibrosis (CF) patients. However, very little is known regarding the fraction of systemically administered antibiotics reaching the lower respiratory tract secretions. We developed and validated amethod to measure the concentrations of piperacillin, ceftazidime, meropenem and aztreonamin CF sputum, and present the validation data. Methods: Ultra-performance LC coupled to tandem MS was used. A single sample can be measured in 2.5 min with multiple reaction monitoring in positive electrospray ionization mode. Deuterated internal standards were used and a concentration range of 0.7-160 mg/L was covered. The method was validated according to the EMA guideline on analytical method validation. Results: The boundaries within which a reliable measurement in CF sputum can be performed were determined. A few constraints are linked to the instability of the antibiotics in sputum. Piperacillin showed limited stability at room temperature and during freeze-thaw cycles. Autosampler instability was observed after 15 h for aztreonam at low concentrations. Conclusions: The method allows a reliable measurement of the selected antibiotics, if precautions are taken regarding the limited stability of piperacillin at room temperature. Due to freeze-thaw instability, piperacillin should always be analysed on the day of sampling. Quick review of the analytical data and reanalysis are needed as low concentrations of aztreonam are not stable in the autosampler. |
| Databáze: | OpenAIRE |
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