A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib
Ibrutinib (IBR) is an oral anticancer medication that inhibits Bruton tyrosine kinase irreversibly. Due to the high risk of adverse effects and its pharmacokinetic variability, the safe and effective use of IBR is expected to be facilitated by precision dosing. Delivering suitable clinical laborator...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/15/4766 |
| _version_ | 1827602098143887360 |
|---|---|
| author | Gellért Balázs Karvaly István Vincze Alexandra Balogh Zoltán Köllő Csaba Bödör Barna Vásárhelyi |
| author_facet | Gellért Balázs Karvaly István Vincze Alexandra Balogh Zoltán Köllő Csaba Bödör Barna Vásárhelyi |
| author_sort | Gellért Balázs Karvaly |
| collection | DOAJ |
| description | Ibrutinib (IBR) is an oral anticancer medication that inhibits Bruton tyrosine kinase irreversibly. Due to the high risk of adverse effects and its pharmacokinetic variability, the safe and effective use of IBR is expected to be facilitated by precision dosing. Delivering suitable clinical laboratory information on IBR is a prerequisite of constructing fit-for-purpose population and individual pharmacokinetic models. The validation of a dedicated high-throughput method using liquid chromatography–mass spectrometry is presented for the simultaneous analysis of IBR and its pharmacologically active metabolite dihydrodiol ibrutinib (DIB) in human plasma. The 6 h benchtop stability of IBR, DIB, and the active moiety (IBR + DIB) was assessed in whole blood and in plasma to identify any risk of degradation before samples reach the laboratory. In addition, four regression algorithms were tested to determine the optimal assay error equations of IBR, DIB, and the active moiety, which are essential for the correct estimation of the error of their future nonparametric pharmacokinetic models. The noncompartmental pharmacokinetic properties of IBR and the active moiety were evaluated in three patients diagnosed with chronic lymphocytic leukemia to provide a proof of concept. The presented methodology allows clinical laboratories to efficiently support pharmacokinetics-based precision pharmacotherapy with IBR. |
| first_indexed | 2024-03-09T05:11:10Z |
| format | Article |
| id | doaj.art-8edf52f11d1b4781ad1e50d2ef73d53b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T05:11:10Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8edf52f11d1b4781ad1e50d2ef73d53b2023-12-03T12:49:34ZengMDPI AGMolecules1420-30492022-07-012715476610.3390/molecules27154766A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol IbrutinibGellért Balázs Karvaly0István Vincze1Alexandra Balogh2Zoltán Köllő3Csaba Bödör4Barna Vásárhelyi5Department of Laboratory Medicine, Semmelweis University, 4 Nagyvárad tér, 1089 Budapest, HungaryDepartment of Laboratory Medicine, Semmelweis University, 4 Nagyvárad tér, 1089 Budapest, HungaryDepartment of Internal Medicine and Hematology, Semmelweis University, 46 Szentkirályi Utca, 1088 Budapest, HungaryDepartment of Laboratory Medicine, Semmelweis University, 4 Nagyvárad tér, 1089 Budapest, HungaryDepartment of Pathology and Experimental Cancer Research, Semmelweis University, 26 Üllői út, 1085 Budapest, HungaryDepartment of Laboratory Medicine, Semmelweis University, 4 Nagyvárad tér, 1089 Budapest, HungaryIbrutinib (IBR) is an oral anticancer medication that inhibits Bruton tyrosine kinase irreversibly. Due to the high risk of adverse effects and its pharmacokinetic variability, the safe and effective use of IBR is expected to be facilitated by precision dosing. Delivering suitable clinical laboratory information on IBR is a prerequisite of constructing fit-for-purpose population and individual pharmacokinetic models. The validation of a dedicated high-throughput method using liquid chromatography–mass spectrometry is presented for the simultaneous analysis of IBR and its pharmacologically active metabolite dihydrodiol ibrutinib (DIB) in human plasma. The 6 h benchtop stability of IBR, DIB, and the active moiety (IBR + DIB) was assessed in whole blood and in plasma to identify any risk of degradation before samples reach the laboratory. In addition, four regression algorithms were tested to determine the optimal assay error equations of IBR, DIB, and the active moiety, which are essential for the correct estimation of the error of their future nonparametric pharmacokinetic models. The noncompartmental pharmacokinetic properties of IBR and the active moiety were evaluated in three patients diagnosed with chronic lymphocytic leukemia to provide a proof of concept. The presented methodology allows clinical laboratories to efficiently support pharmacokinetics-based precision pharmacotherapy with IBR.https://www.mdpi.com/1420-3049/27/15/4766tyrosine kinase inhibitorliquid chromatography–mass spectrometryactive metabolitetherapeutic drug monitoringchronic lymphocytic leukemiaassay error equation |
| spellingShingle | Gellért Balázs Karvaly István Vincze Alexandra Balogh Zoltán Köllő Csaba Bödör Barna Vásárhelyi A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib Molecules tyrosine kinase inhibitor liquid chromatography–mass spectrometry active metabolite therapeutic drug monitoring chronic lymphocytic leukemia assay error equation |
| title | A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib |
| title_full | A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib |
| title_fullStr | A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib |
| title_full_unstemmed | A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib |
| title_short | A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib |
| title_sort | high throughput clinical laboratory methodology for the therapeutic monitoring of ibrutinib and dihydrodiol ibrutinib |
| topic | tyrosine kinase inhibitor liquid chromatography–mass spectrometry active metabolite therapeutic drug monitoring chronic lymphocytic leukemia assay error equation |
| url | https://www.mdpi.com/1420-3049/27/15/4766 |
| work_keys_str_mv | AT gellertbalazskarvaly ahighthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT istvanvincze ahighthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT alexandrabalogh ahighthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT zoltankollo ahighthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT csababodor ahighthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT barnavasarhelyi ahighthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT gellertbalazskarvaly highthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT istvanvincze highthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT alexandrabalogh highthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT zoltankollo highthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT csababodor highthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib AT barnavasarhelyi highthroughputclinicallaboratorymethodologyforthetherapeuticmonitoringofibrutinibanddihydrodiolibrutinib |