Novel high-performance liquid chromatography–tandem mass spectrometry method for simultaneous quantification of BCR-ABL and Bruton’s tyrosine kinase inhibitors and their three active metabolites in human plasma
| Autor: | Yuji Mukai, Nobuo Inotsume, Takeshi Kondo, Tatsunari Yoshida, Takaki Toda |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adolescent
Clinical Biochemistry Dasatinib Fusion Proteins bcr-abl Antineoplastic Agents 030226 pharmacology & pharmacy 01 natural sciences Biochemistry Analytical Chemistry Matrix (chemical analysis) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Limit of Detection Tandem Mass Spectrometry hemic and lymphatic diseases Nitriles Agammaglobulinaemia Tyrosine Kinase medicine Humans Bruton's tyrosine kinase Protein Kinase Inhibitors Chromatography High Pressure Liquid Active metabolite Aniline Compounds Chromatography biology 010401 analytical chemistry Ponatinib Reproducibility of Results Cell Biology General Medicine 0104 chemical sciences chemistry Nilotinib Ibrutinib Linear Models Quinolines biology.protein Drug Monitoring Tyrosine kinase medicine.drug |
| Zdroj: | Journal of Chromatography B. 1137:121928 |
| ISSN: | 1570-0232 |
| DOI: | 10.1016/j.jchromb.2019.121928 |
| Popis: | Therapeutic drug monitoring is important in patients taking BCR-ABL and Bruton’s tyrosine kinase inhibitors (TKIs). Some TKI active metabolites with long elimination half-lives, such as dihydrodiol ibrutinib (DHI), N-desmethyl imatinib (N-DI), and N-desmethyl ponatinib (N-DP), have been characterized, indicating that these active metabolites should be monitored along with the parent compounds. However, there are currently no methods for the simultaneous quantification of BCR-ABL and Bruton’s TKIs and their three active metabolites. The present study aimed to develop and validate a method for the simultaneous quantification of nine pharmacologically active compounds (bosutinib, dasatinib, DHI, ibrutinib, imatinib, N-DI, N-DP, nilotinib, and ponatinib) using high-performance liquid chromatography–tandem mass spectrometry. A 150-μL sample of plasma was analyzed after purification with supported liquid extraction. The method has a run time of 7 min and was successfully validated over the following calibration ranges: 0.25–75 ng/mL for N-DP, 0.5–150 ng/mL for dasatinib and ponatinib, 10–3000 ng/mL for imatinib and nilotinib, and 1–300 ng/mL for the other analytes. Stability of the analytes after short- and long-term storage in the presence of plasma matrix was examined, and all analytes were found to be stable under all tested conditions. The recovery was ≥83%, and the relative standard deviation of internal-standard normalized matrix effects ranged from 3.9 to 13.9%. Dilution integrity up to 4-fold was ensured. The applicability of the method for all analytes was demonstrated using patient samples. |
| Databáze: | OpenAIRE |
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