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PLoS One. 2015 Nov 23;10(11):e0143421. doi: 10.1371/journal.pone.0143421. eCollection 2015.

A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

Author information

1
Laboratorio de Farmacología, Instituto Nacional de Pediatría, Mexico City, Mexico.
2
Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City, Mexico.
3
Servicio de Oncología, Instituto Nacional de Pediatría, Mexico City, Mexico.
4
Laboratorio de Neuropatología, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
5
Laboratorio de Genómica del Cáncer, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
6
Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
7
Unidad de Vigilancia Epidemiológica, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.

Abstract

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. Acetonitrile 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 x 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 cyclophosphamide (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-Q75 29.0) 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.

PMID:
26600181
PMCID:
PMC4657950
DOI:
10.1371/journal.pone.0143421
[Indexed for MEDLINE]
Free PMC Article

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