Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment
Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2− breast cancer treatment. H...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/5/614 |
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| author | Lu Turković Luka Bočkor Oscar Ekpenyong Tajana Silovski Mila Lovrić Slaven Crnković Biljana Nigović Miranda Sertić |
| author_facet | Lu Turković Luka Bočkor Oscar Ekpenyong Tajana Silovski Mila Lovrić Slaven Crnković Biljana Nigović Miranda Sertić |
| author_sort | Lu Turković |
| collection | DOAJ |
| description | Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2− breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors’ peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between −1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between −14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2− breast cancer. |
| first_indexed | 2024-03-10T03:09:57Z |
| format | Article |
| id | doaj.art-dcfbcf8acf4e4afca0b9fe4d003c2a2a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:09:57Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-dcfbcf8acf4e4afca0b9fe4d003c2a2a2023-11-23T12:35:25ZengMDPI AGPharmaceuticals1424-82472022-05-0115561410.3390/ph15050614Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer TreatmentLu Turković0Luka Bočkor1Oscar Ekpenyong2Tajana Silovski3Mila Lovrić4Slaven Crnković5Biljana Nigović6Miranda Sertić7Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, CroatiaCentre for Applied Bioanthropology, Institute for Anthropological Research, Ljudevita Gaja 32, 10000 Zagreb, CroatiaADME & Discovery Toxicology, Merck & Co., Inc., South San Francisco, CA 94080, USADepartment of Oncology, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, CroatiaDepartment of Laboratory Diagnostics, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, CroatiaLudwig Boltzmann Institute for Lung and Vascular Research, Neue Stiftingtalstrasse 6/V, 8010 Graz, AustriaDepartment of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, CroatiaDepartment of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, CroatiaPalbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2− breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors’ peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between −1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between −14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2− breast cancer.https://www.mdpi.com/1424-8247/15/5/614CDK4/6 inhibitorsbreast cancerpalbociclibribociclibabemaciclibanastrozole |
| spellingShingle | Lu Turković Luka Bočkor Oscar Ekpenyong Tajana Silovski Mila Lovrić Slaven Crnković Biljana Nigović Miranda Sertić Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment Pharmaceuticals CDK4/6 inhibitors breast cancer palbociclib ribociclib abemaciclib anastrozole |
| title | Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment |
| title_full | Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment |
| title_fullStr | Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment |
| title_full_unstemmed | Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment |
| title_short | Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment |
| title_sort | development and validation of a novel lc ms ms method for the simultaneous determination of abemaciclib palbociclib ribociclib anastrozole letrozole and fulvestrant in plasma samples a prerequisite for personalized breast cancer treatment |
| topic | CDK4/6 inhibitors breast cancer palbociclib ribociclib abemaciclib anastrozole |
| url | https://www.mdpi.com/1424-8247/15/5/614 |
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