During the lactation, the choice of a proper antibiotic is crucial since the drug can cross into breast milk causing toxicity to the infant. Therefore, an extraction protocol and LC/MS-MS method for the determination of daptomycin in human milk and plasma were developed, validated and applied to a case of a breastfeeding mother affected by a purulent acute soft skin infection treated with daptomycin. Because of daptomycin high protein binding and its high molecular weight, the optimisation of the extraction protocol and analytical conditions were deeply investigated, and several parameters were taken into account: in particular the type of extraction, internal standard, the type of organic modifier, pH of the aqueous solution, and gradient. The use of a protein precipitation protocol coupled to a C8-reverse phase LC-MS/MS allows for a reliable quantification of daptomycin in both plasma (in the range of 19–199 μg/mL) and breast milk (in the range of 0.12–0.32 μg/mL). The determination of milk/plasma (M/P) ratio, which ranged from 0.002 to 0.006, allowed to assess that daptomycin, effective for the mother, was contemporarily safe for the breastfed newborn.

Determination of daptomycin in human plasma and breast milk by UPLC/MS-MS / M. Dei Cas, E. Casagni, V. Gambaro, E. Cesari, G. Roda. - In: JOURNAL OF CHROMATOGRAPHY. B. - ISSN 1570-0232. - 1116(2019), pp. 38-43. [10.1016/j.jchromb.2019.03.036]

Determination of daptomycin in human plasma and breast milk by UPLC/MS-MS

M. Dei Cas
Primo
;
E. Casagni
Secondo
;
V. Gambaro;E. Cesari
Penultimo
;
G. Roda
Ultimo
2019

Abstract

During the lactation, the choice of a proper antibiotic is crucial since the drug can cross into breast milk causing toxicity to the infant. Therefore, an extraction protocol and LC/MS-MS method for the determination of daptomycin in human milk and plasma were developed, validated and applied to a case of a breastfeeding mother affected by a purulent acute soft skin infection treated with daptomycin. Because of daptomycin high protein binding and its high molecular weight, the optimisation of the extraction protocol and analytical conditions were deeply investigated, and several parameters were taken into account: in particular the type of extraction, internal standard, the type of organic modifier, pH of the aqueous solution, and gradient. The use of a protein precipitation protocol coupled to a C8-reverse phase LC-MS/MS allows for a reliable quantification of daptomycin in both plasma (in the range of 19–199 μg/mL) and breast milk (in the range of 0.12–0.32 μg/mL). The determination of milk/plasma (M/P) ratio, which ranged from 0.002 to 0.006, allowed to assess that daptomycin, effective for the mother, was contemporarily safe for the breastfed newborn.
Daptomycin; Human milk; Extraction; LC/MS-MS; Soft skin infection
Settore CHIM/08 - Chimica Farmaceutica
2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/650392
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