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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

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Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, Croatia
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Centre for Applied Bioanthropology, Institute for Anthropological Research, Ljudevita Gaja 32, 10000 Zagreb, Croatia
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ADME & Discovery Toxicology, Merck & Co., Inc., South San Francisco, CA 94080, USA
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Department of Oncology, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia
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Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia
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Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, Croatia
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Ludwig Boltzmann Institute for Lung and Vascular Research, Neue Stiftingtalstrasse 6/V, 8010 Graz, Austria
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Division of Physiology, Medical University of Graz, 8010 Graz, Austria
*
Author to whom correspondence should be addressed.
Academic Editor: Maria Matilde Soares Duarte Marques
Pharmaceuticals 2022, 15(5), 614; https://doi.org/10.3390/ph15050614
Received: 5 April 2022 / Revised: 12 May 2022 / Accepted: 13 May 2022 / Published: 16 May 2022
(This article belongs to the Section Pharmacology)
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. View Full-Text
Keywords: CDK4/6 inhibitors; breast cancer; palbociclib; ribociclib; abemaciclib; anastrozole; letrozole; fulvestrant; therapeutic drug monitoring; LC-MS CDK4/6 inhibitors; breast cancer; palbociclib; ribociclib; abemaciclib; anastrozole; letrozole; fulvestrant; therapeutic drug monitoring; LC-MS
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MDPI and ACS Style

Turković, L.; Bočkor, L.; Ekpenyong, O.; Silovski, T.; Lovrić, M.; Crnković, S.; Nigović, B.; Sertić, M. 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 2022, 15, 614. https://doi.org/10.3390/ph15050614

AMA Style

Turković L, Bočkor L, Ekpenyong O, Silovski T, Lovrić M, Crnković S, Nigović B, Sertić M. 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. 2022; 15(5):614. https://doi.org/10.3390/ph15050614

Chicago/Turabian Style

Turković, Lu, Luka Bočkor, Oscar Ekpenyong, Tajana Silovski, Mila Lovrić, Slaven Crnković, Biljana Nigović, and Miranda Sertić. 2022. "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 15, no. 5: 614. https://doi.org/10.3390/ph15050614

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