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.
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Madhyastha N, Samantha SK, Dittakavi S, Markose M, Mallurwar SR, Zainuddin M, Mullangi R
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. 2021 Apr;35(4):e5043. doi: 10.1002/bmc.5043. Epub 2021 Jan 19.
- PubMed ID
- 33283304 [ View in PubMed]
- Abstract
AMG 510 is the first-in-class KRAS(G12C) 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 acid:acetonitrile; 25:75, 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 --> Q3) m/z 561.1 --> 134.1 and m/z 566.5 --> 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Sotorasib GTPase KRas Protein Humans YesInhibitorDetails