An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum
Background: Abemaciclib is a new oral targeted treatment option for patients with advanced breast cancer. The emerging field of oral antitumor therapeutics presents challenges for both patients and healthcare teams; non-adherence and high inter-individual pharmacokinetic variability can influence re...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Journal of Mass Spectrometry and Advances in the Clinical Lab |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667145X22000025 |
| _version_ | 1811255571844694016 |
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| author | Katharina Habler Michael Vogeser Daniel Teupser |
| author_facet | Katharina Habler Michael Vogeser Daniel Teupser |
| author_sort | Katharina Habler |
| collection | DOAJ |
| description | Background: Abemaciclib is a new oral targeted treatment option for patients with advanced breast cancer. The emerging field of oral antitumor therapeutics presents challenges for both patients and healthcare teams; non-adherence and high inter-individual pharmacokinetic variability can influence response rates. Methods: For monitoring abemaciclib in human sera, a rapid novel ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and fully validated. Sample preparation was based on a protein precipitation step followed by on-line solid phase extraction. Chromatographic separation was achieved using a biphenyl column and the isotope labeled standard abemaciclib-d8 was used for quantification. Results: The method showed linearity over a wide calibration range from 20.0 to 2500 ng/mL. With accuracies and precisions of ≤13.9% and ≤4.42%, respectively, the validation results were within the criteria of acceptance. The fitness of the method was tested by monitoring abemaciclib levels under compassionate use for a single individual. Conclusions: The novelty of the presented two dimensional isotope dilution UHPLC-MS/MS method is in the semi-automated sample preparation, which results in negligible matrix effects, thereby allowing the introduction of abemaciclib into robust routine therapeutic drug monitoring (TDM). This method provides an efficient tool to verify the usefulness of personalized anticancer therapy in clinical practice. |
| first_indexed | 2024-04-12T17:25:53Z |
| format | Article |
| id | doaj.art-ef02efbbad5d47b9818f4e6316369827 |
| institution | Directory Open Access Journal |
| issn | 2667-145X |
| language | English |
| last_indexed | 2024-04-12T17:25:53Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Mass Spectrometry and Advances in the Clinical Lab |
| spelling | doaj.art-ef02efbbad5d47b9818f4e63163698272022-12-22T03:23:18ZengElsevierJournal of Mass Spectrometry and Advances in the Clinical Lab2667-145X2022-04-01241521An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serumKatharina Habler0Michael Vogeser1Daniel Teupser2Corresponding author.; Institute of Laboratory Medicine, University Hospital, LMU Munich, GermanyInstitute of Laboratory Medicine, University Hospital, LMU Munich, GermanyInstitute of Laboratory Medicine, University Hospital, LMU Munich, GermanyBackground: Abemaciclib is a new oral targeted treatment option for patients with advanced breast cancer. The emerging field of oral antitumor therapeutics presents challenges for both patients and healthcare teams; non-adherence and high inter-individual pharmacokinetic variability can influence response rates. Methods: For monitoring abemaciclib in human sera, a rapid novel ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and fully validated. Sample preparation was based on a protein precipitation step followed by on-line solid phase extraction. Chromatographic separation was achieved using a biphenyl column and the isotope labeled standard abemaciclib-d8 was used for quantification. Results: The method showed linearity over a wide calibration range from 20.0 to 2500 ng/mL. With accuracies and precisions of ≤13.9% and ≤4.42%, respectively, the validation results were within the criteria of acceptance. The fitness of the method was tested by monitoring abemaciclib levels under compassionate use for a single individual. Conclusions: The novelty of the presented two dimensional isotope dilution UHPLC-MS/MS method is in the semi-automated sample preparation, which results in negligible matrix effects, thereby allowing the introduction of abemaciclib into robust routine therapeutic drug monitoring (TDM). This method provides an efficient tool to verify the usefulness of personalized anticancer therapy in clinical practice.http://www.sciencedirect.com/science/article/pii/S2667145X22000025Oral tumor therapyKinase inhibitorAbemaciclibTherapeutic drug monitoringTwo dimensional-chromatographyisotope dilution UHPLC-MS/MS |
| spellingShingle | Katharina Habler Michael Vogeser Daniel Teupser An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum Journal of Mass Spectrometry and Advances in the Clinical Lab Oral tumor therapy Kinase inhibitor Abemaciclib Therapeutic drug monitoring Two dimensional-chromatography isotope dilution UHPLC-MS/MS |
| title | An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum |
| title_full | An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum |
| title_fullStr | An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum |
| title_full_unstemmed | An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum |
| title_short | An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum |
| title_sort | uhplc ms ms method for quantification of the cdk4 6 inhibitor abemaciclib in human serum |
| topic | Oral tumor therapy Kinase inhibitor Abemaciclib Therapeutic drug monitoring Two dimensional-chromatography isotope dilution UHPLC-MS/MS |
| url | http://www.sciencedirect.com/science/article/pii/S2667145X22000025 |
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