Abstract:
BACKGROUND:Therapeutic drug monitoring (TDM) of the widely prescribed antidepressant fluoxetine (FLU) is recommended in certain situations, such as occurrence of toxicity, inadequate response or suspect of poor adherence. Dried blood spot (DBS) sampling is an increasingly studied alternative for TDM, particularly for outpatients, due to its ease of collection and inherent stability. OBJECTIVES:The aim of this study was to develop and validate an LC-MS/MS assay for the simultaneous quantification of FLU and norfluoxetine (NFLU) in DBS. DESIGN AND METHODS:The assay is based on a liquid extraction of single DBS with 8mm of diameter, using FLU-D6 as the internal standard, followed by reversed phase separation in an Accucore® C18 column (100×2.1mm, 2.6μm). Mobile phase was composed of water and acetonitrile (gradient from 80:20 to 50:50, v/v), both containing formic acid 0.1%. The assay was validated and applied to 30 patients under FLU pharmacotherapy. RESULTS:The assay was linear in the range 10-750ngmL-1. Precision assays presented CV% of 3.13-9.61 and 3.54-7.99 for FLU and NFLU, respectively, and accuracy in the range of 97.98-110.44% and 100.25-105.8%. FLU and NFLU were stable at 25 and 45°C for 7days. The assay was evaluated in 30 patients under FLU treatment. Concentrations of both compounds were higher in DBS than in plasma, and the use of the multiplying factors 0.71 and 0.68 for FLU and NFLU, respectively, allowed acceptable estimation of plasma concentrations, with median prediction bias of -0.55 to 0.55% and mean differences of 0.4 to 2.2ngmL-1. CONCLUSIONS:The presented data support the clinical use of DBS for therapeutic drug monitoring of FLU.
journal_name
Clin Biochemjournal_title
Clinical biochemistryauthors
da Silva ACC,Raasch JR,Vargas TG,Peteffi GP,Hahn RZ,Antunes MV,Perassolo MS,Linden Rdoi
10.1016/j.clinbiochem.2017.10.002subject
Has Abstractpub_date
2018-02-01 00:00:00pages
85-93eissn
0009-9120issn
1873-2933pii
S0009-9120(17)30794-4journal_volume
52pub_type
杂志文章abstract::Two studies are described in this paper for the purpose of extending the application of the Dupont ACA glucose method to (1) analysis of specimens containing sodium fluoride and sodium iodoacetate, and (2) analysis of specimens containing EDTA, provided analysis is conducted immediately following specimen collection a...
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journal_title:Clinical biochemistry
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journal_title:Clinical biochemistry
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doi:10.1016/j.clinbiochem.2016.01.014
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journal_title:Clinical biochemistry
pub_type: 杂志文章
doi:10.1016/j.clinbiochem.2012.07.098
更新日期:2012-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.clinbiochem.2006.04.020
更新日期:2006-07-01 00:00:00
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doi:10.1016/s0009-9120(77)92784-9
更新日期:1977-10-01 00:00:00
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doi:10.1016/j.clinbiochem.2015.06.016
更新日期:2015-11-01 00:00:00
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doi:10.1016/0009-9120(95)02016-0
更新日期:1996-02-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2003-09-01 00:00:00
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journal_title:Clinical biochemistry
pub_type: 杂志文章
doi:10.1016/j.clinbiochem.2008.06.016
更新日期:2008-10-01 00:00:00
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journal_title:Clinical biochemistry
pub_type: 杂志文章
doi:10.1016/s0009-9120(05)80017-7
更新日期:1991-10-01 00:00:00
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journal_title:Clinical biochemistry
pub_type: 杂志文章
doi:10.1016/j.clinbiochem.2009.03.006
更新日期:2009-07-01 00:00:00