A dried blood spot assay with HPLC-MS/MS for the determination of larotrectinib in mouse blood and its application to a pharmacokinetic study.
Biomed Chromatogr
; 34(12): e4953, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32706402
ABSTRACT
Larotrectinib is a first-generation tropomyosin kinase inhibitor, approved for the treatment of solid tumors. In this paper, we present a validated dried blood spot (DBS) method for the quantitation of larotrectinib from mouse blood using HPLC-MS/MS, which was operated under multiple reaction monitoring mode. To the DBS disc cards, acidified methanol enriched with internal standard (IS; enasidenib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of larotrectinib and the IS was achieved on an Atlantis dC18 column using 10 mm ammonium formate-acetonitrile (3070, v/v) delivered at a flow-rate of 0.80 ml/min. Under these optimized conditions, the retention times of larotrectinib and the IS were ~0.93 and 1.37 min, respectively. The total run time was 2.50 min. Larotrectinib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transitions of 429.1 â 342.1 and 474.1 â 267.1, respectively, were used for the quantitation. The calibration range was 1.06-5,080 ng/ml. No matrix effect or carryover was observed. Hematocrit did not influence DBS larotrectinib concentrations. All of the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mouse pharmacokinetic study.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Pirimidinas
/
Cromatografía Líquida de Alta Presión
/
Espectrometría de Masas en Tándem
/
Pruebas con Sangre Seca
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Chromatogr
Año:
2020
Tipo del documento:
Article
País de afiliación:
India