Development and validation of a high throughput bioanalytical UPLC-MS/MS method for simultaneous determination of tamoxifen and sulphoraphane in rat plasma: Application to an oral pharmacokinetic study.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1152: 122260, 2020 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-32679526
ABSTRACT
Tamoxifen (TAM) is the choice of a drug approved by the Food and Drug Administration (FDA) for the treatment of estrogen-positive receptor (ER+) breast cancer. Sulphoraphane (SFN), a natural plant antioxidant compound, also acts on estrogen-positive breast cancer receptor. Thus, a combination of TAM with SFN is preferred as it helps to minimize the drug-related toxicity and increases the therapeutic efficacy by providing synergistic anticancer effects of both drugs. In the present study, a new simple, sensitive, precise, and selective UPLC-MS/MS method was developed for the simultaneous quantification of tamoxifen and sulphoraphane using propranolol as an internal standard (IS) in rat plasma. Chromatographic separation was achieved on reverse phase Acquity UPLC BEH C18 column (50 mm × 2.1 mm, i.d., 1.7 µm) with an isocratic mobile phase composed of solvent A (0.1% formic acid in acetonitrile) and B (0.1% formic acid in water) (8020, v/v) at a flow-rate of 0.4 mL/min. The detection and quantification of analytes was performed on Waters ZsprayTM Xevo TQD using selected-ion monitoring operated under a positive electrospray ionization mode. The transitions were m/z = 372.0 [M+H]+ â 71.92 for tamoxifen, m/z = 177.9 [M+H]+ â 113.9 for sulphoraphane and m/z = 260.3 [M+H]+ â 116.1 for propranolol. The method was linear over the concentration range of 8-500 ng/mL (r2 = 0.9996) for tamoxifen, 30-2000 ng/mL (r2 = 0.9998) for sulphoraphane with insignificant matrix effect and high extraction recovery on spiked quality control (QC) samples. The intra- and inter-batch precisions and accuracy were within the acceptable limits, and both the analytes were found to be stable throughout the short term, long term and freeze thaw stability studies. The validated method was successfully applied for the simultaneous estimation of TAM and SFN in an oral pharmacokinetic study in female Wistar rats. This developed UPLC-MS/MS method could be a valuable tool for future pharmacokinetic interaction, therapeutic drug monitoring and pharmacokinetic characterization of novel formulations.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sulfóxidos
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Tamoxifeno
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Cromatografia Líquida de Alta Pressão
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Isotiocianatos
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Espectrometria de Massas em Tandem
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article