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Título : A new method to quantify ifosfamide blood levels using dried blood spots and UPLC-MS/MS in paediatric patients with embryonic solid tumours
Creador: Torres Espíndola, Luz María
Nivel de acceso: Open access
Palabras clave : Adolescente Niño
Preescolar
Cromatografía Líquida de Alta Presión - métodos
Ciclofosfamida
Demografía
Pruebas con Sangre Seca - métodos
Femenino
Hematócrito
Humanos
Ifosfamida - sangre
Lactante
Recién nacido
Masculino
Neoplasias de Células Germinales y Embrionarias - sangre
Reproducibilidad de Resultados
Espectrometría de Masas en Tándem - métodos
Adolescent
Child
Child, Preschool
Chromatography, High Pressure Liquid - methods
Cyclophosphamide
Demography
Dried Blood Spot Testing - methods
Female
Hematocrit
Humans
Ifosfamide - blood
Infant
Infant, Newborn
Male
Neoplasms, Germ Cell and Embryonal - blood
Reproducibility of Results
Tandem Mass Spectrometry - methods
Ifosfamida
Ciclofosfamida
sangre
niño
cromatografía
Tumor de Célula Germinal
Espectrometría de Masa en Tándem
Ifosfamide
Cyclophosphamide
blood
child
Chromatography
Neoplasms, Germ Cell and Embryonal
Tandem Mass Spectrometry
Descripción : Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Aceto-nitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 × 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol: acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclo-phosphamide (internal standard). This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4-Q7529.0) and 3.8 μmol/L (Q25 1.5-Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients. © 2015 Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Colaborador(es) u otros Autores: Rivera-Espinosa L
Chávez-Pacheco JL
Navas Cf
Demetrio Ja
Alemón-Medina R
Trujillo F
Pérez M
Zapata M
Cárdenas R
Salinas C
Arnoldo Ar
Velázquez Cr
Castillejos Mj.
Fecha de publicación : 2015
Tipo de publicación: Artículo
Formato: pdf
Identificador del Recurso : 10.1371/journal.pone.0143421
Fuente: Plos One 10(11):1-13
URI : http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2143
Idioma: eng
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