Validated HPLC-MS/MS method for quantitation of AMG 510, a KRAS G12C inhibitor, in mouse plasma and its application to a pharmacokinetic study in mice.
Biomed Chromatogr
; 35(4): e5043, 2021 Apr.
Article
in En
| MEDLINE
| ID: mdl-33283304
ABSTRACT
AMG 510 is the first-in-class KRASG12C inhibitor, currently in phase 2 clinical trials as an orphan drug to treat non-small cell lung cancer patients. We developed and validated a sensitive, selective, and high-throughput HPLC-MS/MS method for the quantitation of AMG 510 in mouse plasma per the regulatory guideline of the US Food and Drug and Administration. AMG 510 and the IS (MRTX-1257) were extracted from mouse plasma using tert-butyl methyl ether and chromatographed using an isocratic mobile phase (0.2% formic acidacetonitrile; 2575, v/v) at a flow rate of 0.65 mL/min on an Atlantis dC18 column. AMG 510 and the IS eluted at ~0.95 and 0.73 min, respectively. AMG 510 and the IS were detected by positive electrospray ionization in multiple reaction monitoring using transition pair (Q1 â Q3) m/z 561.1 â 134.1 and m/z 566.5 â 98.2, respectively. Excellent linearity was achieved in the concentration range of 1.08-5040 ng/mL (r > 0.0996). No matrix effect and carryover were observed. Intra- and inter-day accuracies and precisions were within the acceptance range. AMG 510 was demonstrated to be stable under the tested storage conditions. This novel method has been applied to a pharmacokinetic study in mice.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Piperazines
/
Pyridines
/
Pyrimidines
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Chromatography, High Pressure Liquid
/
Tandem Mass Spectrometry
Type of study:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biomed Chromatogr
Year:
2021
Document type:
Article
Affiliation country:
India
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM