A validated LC-MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay.
Biomed Chromatogr
; 32(8): e4240, 2018 Aug.
Article
en En
| MEDLINE
| ID: mdl-29529709
ABSTRACT
An accurate and sensitive LC-MS/MS method for determining thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in human plasma was developed and validated using umbelliferone as an internal standard. The analytes were extracted from plasma (100 µL) by liquid-liquid extraction with ethyl acetate and then separated on a BETASIL C18 column (4.6 × 150 mm, 5 µm) with mobile phase composed of methanol-water containing 0.1% formic acid (7030, v/v) in isocratic mode at a flow rate of 0.5 mL/min. The detection was performed using an API triple quadrupole mass spectrometer in atmospheric pressure chemical ionization mode. The precursor-to-product ion transitions m/z 259.1 â 186.1 for thalidomide, m/z 273.2 â 161.3 for 5-hydroxy thalidomide, m/z 273.2 â 146.1 for 5'-hydroxy thalidomide and m/z 163.1 â 107.1 for umbelliferone (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentrations of 10.0-2000.0 ng/mL for thalidomide, 0.2-50.0 ng/mL for 5-hydroxy thalidomide and 1.0-200.0 ng/mL for 5'-hydroxy thalidomide. The method was validated with respect to linear, within- and between-batch precision and accuracy, extraction recovery, matrix effect and stability. Then it was successfully applied to estimate the concentration of thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in plasma samples collected from Crohn's disease patients after a single oral administration of thalidomide 100 mg.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Talidomida
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Cromatografía Liquida
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Espectrometría de Masas en Tándem
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Humans
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Male
Idioma:
En
Año:
2018
Tipo del documento:
Article