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

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...

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Main Authors: Leonardo Costalonga Rodrigues, Lílian de Araújo Lima, Débora Zorrón Berlinck, Mariana Vieira Morau, Mauricio Wesley Perroud Junior, Patrícia Moriel, Jose Luiz Costa
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Green Analytical Chemistry
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772577424000867
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author Leonardo Costalonga Rodrigues
Lílian de Araújo Lima
Débora Zorrón Berlinck
Mariana Vieira Morau
Mauricio Wesley Perroud Junior
Patrícia Moriel
Jose Luiz Costa
author_facet Leonardo Costalonga Rodrigues
Lílian de Araújo Lima
Débora Zorrón Berlinck
Mariana Vieira Morau
Mauricio Wesley Perroud Junior
Patrícia Moriel
Jose Luiz Costa
author_sort Leonardo Costalonga Rodrigues
collection DOAJ
description 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-desmethyl-gefitinib. 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 LC-MS/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 °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-desmethyl-gefitinib 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.
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spelling doaj-art-b82bec05d7e745509add2597c4fa0b752024-12-08T06:13:27ZengElsevierGreen Analytical Chemistry2772-57742024-12-0111100177Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MSLeonardo Costalonga Rodrigues0Lílian de Araújo Lima1Débora Zorrón Berlinck2Mariana Vieira Morau3Mauricio Wesley Perroud Junior4Patrícia Moriel5Jose Luiz Costa6Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Campinas, Sao Paulo, 13083-887, Brazil; Universidade Estadual de Campinas (UNICAMP), Centro de Informação e Assistência Toxicológica de Campinas (CIATox-Campinas), Campinas, Sao Paulo, 13083-881, BrazilUniversidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Campinas, Sao Paulo, 13083-887, Brazil; Universidade Estadual de Campinas (UNICAMP), Centro de Informação e Assistência Toxicológica de Campinas (CIATox-Campinas), Campinas, Sao Paulo, 13083-881, BrazilUniversidade Estadual de Campinas (UNICAMP), Centro de Informação e Assistência Toxicológica de Campinas (CIATox-Campinas), Campinas, Sao Paulo, 13083-881, Brazil; Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Farmacêuticas, Campinas, Sao Paulo, 13083-871, BrazilUniversidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Farmacêuticas, Campinas, Sao Paulo, 13083-871, BrazilUniversidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Campinas, Sao Paulo, 13083-887, BrazilUniversidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Farmacêuticas, Campinas, Sao Paulo, 13083-871, BrazilUniversidade Estadual de Campinas (UNICAMP), Centro de Informação e Assistência Toxicológica de Campinas (CIATox-Campinas), Campinas, Sao Paulo, 13083-881, Brazil; Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Farmacêuticas, Campinas, Sao Paulo, 13083-871, Brazil; Corresponding author at: Universidade Estadual de Campinas (UNICAMP), Centro de Informação e Assistência Toxicológica de Campinas (CIATox-Campinas), Campinas, Sao Paulo, 13083-881, Brazil.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-desmethyl-gefitinib. 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 LC-MS/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 °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-desmethyl-gefitinib 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.http://www.sciencedirect.com/science/article/pii/S2772577424000867Solid phase microextraction tipsGefitinibPlasmaTherapeutic drug monitoringGreen analytical toxicologyLC-MS/MS
spellingShingle Leonardo Costalonga Rodrigues
Lílian de Araújo Lima
Débora Zorrón Berlinck
Mariana Vieira Morau
Mauricio Wesley Perroud Junior
Patrícia Moriel
Jose Luiz Costa
Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MS
Green Analytical Chemistry
Solid phase microextraction tips
Gefitinib
Plasma
Therapeutic drug monitoring
Green analytical toxicology
LC-MS/MS
title Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MS
title_full Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MS
title_fullStr Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MS
title_full_unstemmed Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MS
title_short Development and application of solid phase microextraction tips (SPME LC tips) method for therapeutic drug monitoring of gefitinib by LC-MS/MS
title_sort development and application of solid phase microextraction tips spme lc tips method for therapeutic drug monitoring of gefitinib by lc ms ms
topic Solid phase microextraction tips
Gefitinib
Plasma
Therapeutic drug monitoring
Green analytical toxicology
LC-MS/MS
url http://www.sciencedirect.com/science/article/pii/S2772577424000867
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