Direct chiral LC-MS/MS analysis of fexofenadine enantiomers in plasma and urine with application in a maternal-fetal pharmacokinetic study

Autor(es)

Ribeiro Pinto, Leonardo Santos ^[1] ; do Vale, Gabriel Tavares ^[2] ; Moreira, Fernanda de Lima ^[1] ; Marques, Maria Paula ^[1] ; Coelho, Eduardo Barbosa ^[2] ; Cavalli, Ricardo Carvalho ^[3] ; Lanchote, Vera Lucia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Obstet & Ginecol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES; v. 1145, MAY 15 2020.
• Citações Web of Science: 0

Resumo

This study shows the development and validation of two enantioselective LC-MS/MS methods for the determination of fexofenadine in biological matrices including the elution order determination. Plasma (200 mu L) or urine (50 mu L) aliquots were added to the internal standard solution {[}(S)-( - )-metoprololl and extracted in the acid medium with chloroform. Resolution of the (R)-(+)- and (S) (-) fexofenadine enantiomers was performed in a Chirobiotic V column. The methods showed linearity at the range of 0.025-100 mu/mL plasma and 0.02-10 mu g/mL urine for each fexofenadine enantiomer. These methods were applied to the maternal-fetal pharmacokinetics of fexofenadine enantiomers in plasma and urine of parturient women (n = 8) treated with a single oral 60 mg dose of racemic fexofenadine. Enantiomeric ratio in plasma (AUC(0-infinity(R)-(+)- and (S) (-))) was close to 1.5, nevertheless in urine was closed to unity. The transplacental transfer was approximately 18% for both fexofenadine enantiomers. The enantioselective methods can also be useful in future clinical studies of chiral discrimination of drug transporters. (AU)

• Processo FAPESP: 18/05616-3 - Farmacocinética clínica em doenças infecciosas
• Beneficiário: Vera Lúcia Lanchote
• Modalidade de apoio: Auxílio à Pesquisa - Temático