Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability
Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) inhibitor and has a potent antitumor activity against FGFR-aberrant malignancies. Erdafitinib has a narrow therapeutic index, and its pharmacokinetics are influenced by genetic variability and interacting medication. Routine therape...
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MDPI AG
2022-08-01
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| Series: | Applied Sciences |
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| Online Access: | https://www.mdpi.com/2076-3417/12/17/8625 |
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| author | Essam A. Ali Muzaffar Iqbal Gamal A. Mostafa Mohamed R. Alhazani Yousif A. Asiri |
| author_facet | Essam A. Ali Muzaffar Iqbal Gamal A. Mostafa Mohamed R. Alhazani Yousif A. Asiri |
| author_sort | Essam A. Ali |
| collection | DOAJ |
| description | Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) inhibitor and has a potent antitumor activity against FGFR-aberrant malignancies. Erdafitinib has a narrow therapeutic index, and its pharmacokinetics are influenced by genetic variability and interacting medication. Routine therapeutic drug monitoring and dose adjustment are recommended. This study aims at developing a new UPLC-MS/MS method for determination and quantitation of erdafitinib in human plasma using ibrutinib as an internal standard. The sample ionization was performed by using electrospray ionization in positive mode, and multiple reaction monitoring was used for the quantification of target analytes. The chromatographic separation of erdafitinib and IS was achieved by an UPLC BEH C<sub>18</sub> column (2.1 mm × 100 mm, 1.7 μm). Erdafitinib metabolic stability was studied using intrinsic clearance and in vitro half-life. The greenness of the developed method was evaluated using appropriate, analytical Eco-Scale and AGREE software. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.99 with a limit of quantitation of 0.5 ng/mL. The accuracy and precision were within acceptable limits and the average recovery and matrix effects were 86.11% and 90.51%, respectively. Erdafitinib metabolic stability was studied and its in vitro half-life was 7.28 min and intrinsic clearance was 95.11 µL/min/mg. The assessment of the greenness profile of the method indicated that the method is eco-friendly. The proposed method can be utilized for therapeutic drug monitoring and pharmacokinetic studies. |
| first_indexed | 2024-03-10T03:02:50Z |
| format | Article |
| id | doaj.art-85fa745158e94b98bc274b0559bc0b96 |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T03:02:50Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-85fa745158e94b98bc274b0559bc0b962023-11-23T12:42:54ZengMDPI AGApplied Sciences2076-34172022-08-011217862510.3390/app12178625Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic StabilityEssam A. Ali0Muzaffar Iqbal1Gamal A. Mostafa2Mohamed R. Alhazani3Yousif A. Asiri4Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh P.O. Box 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh P.O. Box 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh P.O. Box 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh P.O. Box 11451, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh P.O. Box 11451, Saudi ArabiaErdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) inhibitor and has a potent antitumor activity against FGFR-aberrant malignancies. Erdafitinib has a narrow therapeutic index, and its pharmacokinetics are influenced by genetic variability and interacting medication. Routine therapeutic drug monitoring and dose adjustment are recommended. This study aims at developing a new UPLC-MS/MS method for determination and quantitation of erdafitinib in human plasma using ibrutinib as an internal standard. The sample ionization was performed by using electrospray ionization in positive mode, and multiple reaction monitoring was used for the quantification of target analytes. The chromatographic separation of erdafitinib and IS was achieved by an UPLC BEH C<sub>18</sub> column (2.1 mm × 100 mm, 1.7 μm). Erdafitinib metabolic stability was studied using intrinsic clearance and in vitro half-life. The greenness of the developed method was evaluated using appropriate, analytical Eco-Scale and AGREE software. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.99 with a limit of quantitation of 0.5 ng/mL. The accuracy and precision were within acceptable limits and the average recovery and matrix effects were 86.11% and 90.51%, respectively. Erdafitinib metabolic stability was studied and its in vitro half-life was 7.28 min and intrinsic clearance was 95.11 µL/min/mg. The assessment of the greenness profile of the method indicated that the method is eco-friendly. The proposed method can be utilized for therapeutic drug monitoring and pharmacokinetic studies.https://www.mdpi.com/2076-3417/12/17/8625erdafitinibecofriendlymetabolic stabilityUPLC-MS/MS |
| spellingShingle | Essam A. Ali Muzaffar Iqbal Gamal A. Mostafa Mohamed R. Alhazani Yousif A. Asiri Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability Applied Sciences erdafitinib ecofriendly metabolic stability UPLC-MS/MS |
| title | Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability |
| title_full | Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability |
| title_fullStr | Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability |
| title_full_unstemmed | Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability |
| title_short | Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability |
| title_sort | ecofriendly simple fast and sensitive uplc ms ms method for determination of erdafitinib a novel tyrosine kinase inhibitor in plasma and its application to metabolic stability |
| topic | erdafitinib ecofriendly metabolic stability UPLC-MS/MS |
| url | https://www.mdpi.com/2076-3417/12/17/8625 |
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