Determination of amoxicillin and cotrimoxazole concentrations in sputum of patients with cystic fibrosis.
Camille TronChantal BelleguicCaroline PiauGraziella BrinchaultEric DeneuvilleCharles RicordelSamer KayalEric BellissantMarie-Clémence VerdierFlorian LemaitrePublished in: Biomedical chromatography : BMC (2021)
In the management of cystic fibrosis, treatments against Staphylococcus aureus and Haemophilus influenzae such as amoxicillin or cotrimoxazole have to be prescribed and the antibiotherapy's efficacy may be linked to the concentration that reaches the infected site. As cystic fibrosis patients present disturbed pharmacokinetics parameters, drug monitoring would be relevant to assess the lung distribution of antibiotics and to optimize dosing regimens. In this context, the aim of the study was to develop and validate HPLC-based methods for the determination of both antibiotics in bronchial sputum from cystic fibrosis patients, in order to assess the distribution of the drugs into the lungs. Plasma proteins were precipitated by acetonitrile and amoxicillin concentrations in sputum were determined by HPLC coupled with tandem-mass spectrometry. Following liquid extraction with ethyl acetate, cotrimoxazole was quantified by HPLC using ultraviolet detection. Both methods were rapid, specific, accurate and reproducible. The method was applied to patient samples. In three treated patients, concentrations of amoxicillin in sputum were similar and below the lower limit of quantification (0.1 μg/g) and in six patients, sputum concentrations up to 11.1 and 6.4 μg/g were measured for sulfamethoxazole and trimethoprim, respectively.
Keyphrases
- cystic fibrosis
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- staphylococcus aureus
- mycobacterium tuberculosis
- tandem mass spectrometry
- prognostic factors
- simultaneous determination
- high resolution
- patient reported outcomes
- chronic obstructive pulmonary disease
- air pollution
- wastewater treatment