Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MS

Author(s)

Rodrigues, Leonardo Costalonga ; Lima, Lilian de Araujo ; Berlinck, Debora Zorron ; Morau, Mariana Vieira ; Perroud Junior, Mauricio Wesley ; Moriel, Patricia ; Costa, Jose Luiz

• Document type: Journal article
• Source: GREEN ANALYTICAL CHEMISTRY; v. 11, p. 9-pg., 2024-12-01.

Abstract

Lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). Among the existing therapies for NSCLC, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can be mentioned. Gefitinib is one of the first-generation reversible EGFR-TKIs and its main metabolite is O-desmethylgefitinib. The therapeutic range upper limit for gefitinib has not yet been clearly established despite being an indication of its toxicity, and its adverse drug reaction may be unpredictable. Therefore, therapeutic drug monitoring (TDM) can be applied by measuring gefitinib concentration in blood and its fractions. Solid phase microextraction (SPME) is a miniaturized sample preparation technique, and SPME LC tips represent a variation of SPME. This technique utilizes an inert support coated with HPLC-type silica particles, presenting several advantages. Here, we successfully developed, optimized, and validated a green analytical method for the quantification of gefitinib and its metabolite, O-desmethylgefitinib, in plasma samples, by SPME LC tips and LCMS/MS. Linearity was achieved from 20 to 800 ng/mL and LLOQ of 20 ng/mL. No interferences were seen at selectivity tests. Matrix effect was lower than 22.9 % and inaccuracy, intra-, and inter-run imprecision were better than 15.4 %. No carryover was observed and stability study was successfully applied for processed samples maintained in the autosampler at 10 degrees C for 24 h The method was applied for four authentic samples from individuals under gefitinib treatment, detecting gefitinib from 104.6 ng/mL to 777.1 ng/mL and O-desmethylgefitinib from 85.2 ng/mL to 499.2 ng/mL. Finally, the greenness characteristic was evaluated by three tools, achieving satisfactory results that confirm its compliance to GAC principles. (AU)

• FAPESP's process: 20/10809-5 - Microextraction techniques in forensic toxicology
• Grantee: José Luiz da Costa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/06280-7 - ADVERSE EVENTS OF TREATMENT IN ADVANCED NON-SMALL CELL LUNG CANCER: CONTRIBUTION OF CLINICAL, GENETIC AND EPIGENETIC FACTORS
• Grantee: Patricia Moriel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/11848-4 - Use of solid phase microextraction in tips (SPME-Tips) for analysis of cocaine and biotransformation products in oral fluid by liquid chromatography tandem mass spectrometry (LC-MS / MS)
• Grantee: Leonardo Costalonga Rodrigues
• Support Opportunities: Scholarships in Brazil - Scientific Initiation