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.

中文翻译：

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囊性纤维化患者痰液中阿莫西林和复方新诺明浓度的测定

在囊性纤维化的管理中，针对金黄色葡萄球菌和流感嗜血杆菌的治疗例如阿莫西林或复方新诺明必须开具处方，并且抗生素治疗的功效可能与到达感染部位的浓度有关。由于囊性纤维化患者的药代动力学参数受到干扰，因此药物监测与评估抗生素的肺部分布和优化给药方案有关。在这种情况下，本研究的目的是开发和验证基于 HPLC 的方法，用于测定囊性纤维化患者支气管痰中的两种抗生素，以评估药物在肺部的分布。血浆蛋白用乙腈沉淀，痰液中的阿莫西林浓度通过 HPLC 与串联质谱联用测定。用乙酸乙酯进行液体萃取后，复方新诺明通过使用紫外检测的HPLC定量。两种方法都快速、特异、准确且可重复。该方法应用于患者样本。在 3 名接受治疗的患者中，痰中阿莫西林的浓度相似且低于定量下限 (0.1 μg/g)，在 6 名患者中，磺胺甲恶唑和甲氧苄啶的痰浓度分别高达 11.1 和 6.4 μg/g。