LC–MS/MS-ESI method for simultaneous quantification of darolutamide and its active metabolite, ORM-15341 in mice plasma and its application to a pharmacokinetic study
[Display omitted] •First LC–MS/MS method being reported for the simultaneous quantification of darolutamide and ORM-15341 in mice plasma.•Simple sample processing method and shorter run time (2.5min) enables this method as a high throughput assay.•Method was validated as per regulatory guidelines.•T...
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Published in | Journal of pharmaceutical and biomedical analysis Vol. 145; pp. 454 - 461 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier B.V
25.10.2017
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Subjects | |
Online Access | Get full text |
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Summary: | [Display omitted]
•First LC–MS/MS method being reported for the simultaneous quantification of darolutamide and ORM-15341 in mice plasma.•Simple sample processing method and shorter run time (2.5min) enables this method as a high throughput assay.•Method was validated as per regulatory guidelines.•The method is specific, precise, accurate and no matrix effect was observed.•Method was used in a mice pharmacokinetic study to derive the pharmacokinetic parameters for analytes.
A sensitive and rapid LC–MS/MS method was developed and validated for the simultaneous quantitation of darolutamide and its active metabolite i.e. ORM-15341 in 50μL mice plasma using bicalutamide as an internal standard (I.S.) as per regulatory guidelines. Sample processing was accomplished through liquid-liquid extraction. Chromatographic separation was achieved using an Atlantis C18 column with an isocratic mobile phase comprising 0.2% formic acid:acetonitrile (35:65, v/v) at a flow rate of 0.8mL/min within 2.5min. Detection and quantitation were done by multiple reaction monitoring on a triple quadrupole mass spectrometer following the transitions: m/z 397→202, 395→202 and 429→255 for darolutamide, ORM-15341 and I.S, respectively in the negative ionization mode. The calibration curve was linear from 0.61–1097ng/mL for both darolutamide and ORM-15341. The intra- and inter-day precisions were in the range of 1.34–13.8 and 4.85–12.9 and 3.91–13.7 and 6.54–14.2%, for darolutamide and ORM-15341, respectively. Darolutamide and ORM-15341 were found to be stable under different stability conditions. The validated method was applied to a pharmacokinetic study in mice. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0731-7085 1873-264X |
DOI: | 10.1016/j.jpba.2017.06.074 |