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• W2772180695 abstract "Irinotecan (IRI) is an antineoplastic drug widely used for the treatment of colorectal and advanced pancreatic cancer. Despite its clinical utility, the clinical use of IRI is associated with potentially severe hematopoietic and gastrointestinal toxicities. The quantification of IRI and its active metabolite SN-38 in dried blood spots (DBS) may be an alternative to individualize the drug dose through a minimally invasive and easy collection method. The aim of this study was to develop and validate a simple and fast HPLC-FL assay for simultaneous IRI and SN-38 measurement in DBS, with adequate analytical performance for clinical use. The method employs liquid extraction of one 8 mm disk of whole blood, followed by separation in a reversed phase Eclipse Plus C8 column (150 × 4.6 mm, 5 μm). Detection was performed with a fluorescence detector, with excitation wavelength of 370 and emission of 420 for IRI and 540 nm for SN-38 and internal standard (camptothecin). Total analytical run time was 17 min. Mobile phase was a mixture of 0.1 M phosphate buffer pH 4.0 and acetonitrile (80:20, v/v), at 1 mL min−1. The assay was linear in the range 10–3,000 ng mL−1 and from 0.5 to 300 ng mL−1 for IRI and SN-38, respectively. Precision assays presented CV% of 2.71-5.65 and 2.15-10.07 for IRI and SN-38, respectively, and accuracy in the range of 94.26-100.93 and 94.24-99.33%. IRI and SN-38 were stable at 25 and 42 °C for 14 days in DBS samples. The method was applied to DBS samples obtained from fingerpicks from 19 volunteers receiving IRI in single or combined chemotherapy regimens, collected 1 and 24 h after beginning of the infusion. The estimated plasma concentration of IRI and SN-38 in sample collected 1 h after star of infusion had 16 of 19 values within the ±20% range of the measured plasma concentrations. On the other hand, predictions of IRI and SN-38 plasma concentrations from DBS measurements obtained 24 h after the beginning of the infusion were poor. AUC of IRI that was calculated using plasma and DBS-estimated concentrations, with a high correlation (r = 0.918). The method presented suitable characteristics for the clinical use. However, translation of IRI and SN-38 DBS to plasma concentrations is challenging due to the compound’s variable plasma/blood partition." @default.
• W2772180695 created "2017-12-22" @default.
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• W2772180695 date "2018-02-01" @default.
• W2772180695 modified "2023-10-18" @default.
• W2772180695 title "Determination of irinotecan and its metabolite SN-38 in dried blood spots using high-performance liquid-chromatography with fluorescence detection" @default.
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• W2772180695 doi "https://doi.org/10.1016/j.jpba.2017.11.079" @default.
• W2772180695 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29216585" @default.
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