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Updated: Mar 8, 2026
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Development and validation of LC-MS/MS with in-source collision-induced dissociation for the quantification of
Monique Zangarini1, Neil Rajan2, Marina Danilenko2
1Newcastle Cancer Centre Pharmacology Group, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Aim:
Pegcantratinib is a mini-PEGylated K252a derivative, under clinical evaluation as an anticancer agent acting through inhibition of the tropomyosin receptor kinase. A method for quantifying pegcantratinib in skin tumor biopsies of patients was required to determine tumor drug penetration.
Methods & Results:
A sensitive and PEGylated molecule specific HPLC-MS/MS method coupled with in-source collision-induced dissociation was developed. The method exhibited excellent precision (coefficient of variation ≤8.5%), accuracy in the range 95-102%, high and consistent recovery and no matrix effect. The assay was linear across a range of 1-500 ng/ml, with a limit of quantitation of 2.5 ng/ml.
Conclusion:
We have developed and validated a method for analyzing pegcantratinib in human tumor biopsies, with the approach successfully applied to clinical trial samples.
Insights
A new HPLC-MS/MS method accurately quantifies pegcantratinib in skin tumor biopsies. This validated assay is crucial for assessing anticancer drug penetration in patients during clinical trials.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Oncology
Background:
- Pegcantratinib is a mini-PEGylated K252a derivative investigated as an anticancer agent.
- It functions by inhibiting tropomyosin receptor kinase (TRK).
- Accurate quantification of drug levels in tumor tissue is essential for efficacy studies.
Purpose of the Study:
- To develop and validate a sensitive bioanalytical method.
- Quantify pegcantratinib concentrations in human skin tumor biopsies.
- Determine tumor drug penetration for clinical evaluation.
Main Methods:
- High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
- In-source collision-induced dissociation (CID) for enhanced sensitivity.
- Method validation including linearity, precision, accuracy, recovery, and matrix effect.
Main Results:
- A sensitive and specific HPLC-MS/MS method was developed and validated.
- The assay demonstrated excellent precision (CV ≤8.5%) and accuracy (95-102%).
- Linearity was established from 1-500 ng/ml with a limit of quantitation of 2.5 ng/ml.
Conclusions:
- A robust method for pegcantratinib analysis in human tumor biopsies was successfully developed.
- The validated method was effectively applied to analyze clinical trial samples.
- This assay supports the clinical development of pegcantratinib as an anticancer therapy.
