Simultaneous Quantification of BCR-ABL and Bruton Tyrosine Kinase Inhibitors in Dried Plasma Spots and Its Application to Clinical Sample Analysis
| Autor: | Takeshi Kondo, Yuji Mukai, Nobuo Inotsume, Yuka Yoshida, Takaki Toda, Tatsunari Yoshida |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Dasatinib
Genes abl 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tandem Mass Spectrometry Nitriles medicine Agammaglobulinaemia Tyrosine Kinase Bruton's tyrosine kinase Humans Pharmacology (medical) Protein Kinase Inhibitors Pharmacology Chromatography Aniline Compounds medicine.diagnostic_test biology Ponatinib Imidazoles Pyridazines Pyrimidines Nilotinib chemistry Therapeutic drug monitoring Ibrutinib biology.protein Imatinib Mesylate Quinolines Dried Blood Spot Testing Drug Monitoring Tyrosine kinase Bosutinib medicine.drug Chromatography Liquid |
| Zdroj: | Therapeutic drug monitoring. 43(3) |
| ISSN: | 1536-3694 |
| Popis: | Background Recent reports highlight the importance of therapeutic drug monitoring (TDM) of BCR-ABL and Bruton's tyrosine kinase inhibitors (TKIs); thus, large-scale studies are needed to determine the target concentrations of these drugs. TDM using dried plasma spots (DPS) instead of conventional plasma samples is a promising approach. The present study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of BCR-ABL and Bruton's TKIs for further TDM studies. Methods A 20-μL aliquot of plasma was spotted onto filter paper and dried completely. Analytes were extracted from two DPS using 250 μL of solvent. After clean-up by supported liquid extraction, the sample was analyzed by LC-MS/MS. Applicability of the method was examined using samples of patient DPS transported by regular mail as a proof-of-concept study. The constant bias and proportional error between plasma and DPS concentrations were assessed by Passing-Bablok regression analysis, and systematic errors were evaluated by Bland-Altman analysis. Results The method was successfully validated over the following calibration ranges: 1-200 ng/mL for dasatinib and ponatinib, 2-400 ng/mL for ibrutinib,5-1000 ng/mL for bosutinib, and 20-4000 ng/mL for imatinib and nilotinib. TKI concentrations were successfully determined for 93 of 96 DPS from clinical samples. No constant bias between plasma and DPS concentrations was observed for bosutinib, dasatinib, nilotinib, and ponatinib, whereas there were proportional errors between the plasma and DPS concentrations of nilotinib and ponatinib. Bland-Altman plots revealed that significant systematic errors existed between both methods for bosutinib, nilotinib, and ponatinib. Conclusions An LC-MS/MS method for the simultaneous quantification of six TKIs in DPS was developed and validated. Further large-scale studies should be conducted to assess the consistency of concentration measurements obtained from plasma and DPS. |
| Databáze: | OpenAIRE |
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