Development and validation of an LC-MS/MS method to quantify ceftaroline in microdialysate samples from plasma and brain : application to a preclinical pharmacokinetic investigation

• Autor(a) principal: Helfer, Victória Etges
• Data de Publicação: 2023
• Outros Autores: Dias, Bruna Bernar, Lock, Graziela de Araújo, Tomaszewski, Caroline Andrade, Barnet, Lucas Suchecki, Barreto, Fabiano, Zavascki, Alexandre Prehn, Araújo, Bibiana Verlindo de, Dalla Costa, Teresa Cristina Tavares
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/262958
• topic: Estudo de validação; Plasma; Cérebro; Microdiálise; Farmacocinética; Ceftaroline; Microdialysis; LC-MS/MS; Unbound concentrations; Analytical method validation

A bioanalytical LC–MS/MS method was developed and validated to determine ceftaroline in microdialysate samples from plasma and brain. Ceftaroline was separated using a C18 column and a mobile phase consisting of water and acetonitrile, both with 5 mM of ammonium formate and acid formic 0.1%, eluted as gradient. Ceftaroline was monitored using electrospray ionization operating on positive mode (ESI+) monitoring the transition 604.89 > 209.3 m/z. The method showed linearity in the concentration range of 0.5–500 ng/mL for brain microdialysate and 0.5–2500 ng/mL for plasma microdialysate with coefficients of determination ≥0.997. The inter-and intra-day precision, the accuracy, and the stability of the drug in different conditions were in accordance with the acceptable limits determined by international guidelines. Plasma pharmacokinetics and brain distribution of the drug were carried out after intravenous administration of 20 mg/kg of ceftaroline to male Wistar rats. The estimated geometric mean (geometric coefficient of variation) area under the curve (AUC0-∞) was 4.68 (45.8%) mg·h/L and 1.20 (54.2%) mg·h/L for plasma and brain, respectively, resulting in a brain exposure of about 33% (AUCfree brain/AUCfree plasma). The results indicate that ceftaroline presents good penetration in the brain when considering free plasma and free brain concentrations.