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Development and validation of a UPLC-MS/MS method for quantification of C-005, a novel third-generation EGFR TKI, and
Zhenlei Wang1, Wei Ye1, Yongping Qin1
1GCP Center/Institute of Clinical Pharmacology, West China Hospital of Sichuan University, Chengdu 610041, China.
Abstract:
C-005 is a novel third-generation EGFR tyrosine kinase inhibitor for the treatment of non-small cell lung cancer (NSCLC). To support its clinical trial, we developed a rapid and sensitive bioanalytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique for the quantification of C-005 and its major metabolite in NSCLC patients following international bioanalytical guidelines. After a simple and quick protein precipitation step, the supernatant was injected to a Waters Acquity BEH C18 column (2.1 × 50 mm i.d., 1.7 mm), and the column was eluted with a gradient of buffer A (5 mM ammonium acetate and 0.1% formic acid in water) and buffer B (formic acid-acetonitrile (1:1000, v/v)). The eluates were subsequently detected by an AB QTRAP 5500 mass spectrometer with electrospray ionization using multiple-reaction monitoring mode. The method showed good linearity from 2.00 to 1000 ng/mL for C-005 and 1.00 to 500 ng/mL for M1. In conclusion, the validation results demonstrated the robustness of the method and its well-poised to support the first-in-patient study of C-005 in NSCLC patients.
Insights
A new bioanalytical method quantifies C-005, a novel EGFR inhibitor, and its metabolite in non-small cell lung cancer (NSCLC) patients. This validated UPLC-MS/MS method supports C-005
Area of Science:
- Analytical Chemistry
- Pharmacology
- Oncology
Background:
- Non-small cell lung cancer (NSCLC) treatment involves targeted therapies.
- EGFR tyrosine kinase inhibitors (TKIs) are crucial in NSCLC management.
- Accurate quantification of drugs and metabolites is essential for clinical trials.
Purpose of the Study:
- To develop and validate a sensitive bioanalytical method for C-005 and its major metabolite.
- To support the clinical development of C-005, a third-generation EGFR TKI.
- To ensure reliable quantification in NSCLC patient samples.
Main Methods:
- Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed.
- Protein precipitation was used for sample preparation.
- A Waters Acquity BEH C18 column and AB QTRAP 5500 mass spectrometer were utilized.
Main Results:
- The method demonstrated good linearity for C-005 (2.00–1000 ng/mL) and its metabolite M1 (1.00–500 ng/mL).
- The bioanalytical method was validated according to international guidelines.
- The assay proved to be rapid, sensitive, and robust.
Conclusions:
- The validated UPLC-MS/MS method is suitable for quantifying C-005 and its metabolite in NSCLC patients.
- This method will support the first-in-patient study of C-005.
- The assay's robustness ensures reliable data for clinical trials.
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