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Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples
In the development of bioanalytical LC-MS methods for the determination of drugs in plasma samples in a clinical setting, adequate sample preparation is of utmost importance. The main goals are to achieve the selective extraction of the analytes of interest and attain thorough matrix removal while r...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610126/ https://www.ncbi.nlm.nih.gov/pubmed/37895916 http://dx.doi.org/10.3390/ph16101445 |
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author | Turković, Lu Mutavdžić Pavlović, Dragana Mlinarić, Zvonimir Skenderović, Anamarija Silovski, Tajana Sertić, Miranda |
author_facet | Turković, Lu Mutavdžić Pavlović, Dragana Mlinarić, Zvonimir Skenderović, Anamarija Silovski, Tajana Sertić, Miranda |
author_sort | Turković, Lu |
collection | PubMed |
description | In the development of bioanalytical LC-MS methods for the determination of drugs in plasma samples in a clinical setting, adequate sample preparation is of utmost importance. The main goals are to achieve the selective extraction of the analytes of interest and attain thorough matrix removal while retaining acceptable ecological properties, cost-effectiveness, and high throughput. Solid-phase extraction (SPE) offers a versatile range of options, from the selection of an appropriate sorbent to the optimisation of the washing and elution conditions. In this work, the first SPE method for the simultaneous extraction of six anticancer drugs used in novel therapeutic combinations for advanced breast cancer treatment—palbociclib, ribociclib, abemaciclib, anastrozole, letrozole, and fulvestrant—was developed. The following sorbent chemistries were tested: octylsilyl (C8), octadecylsilyl (C18), hydrophilic–lipophilic balance (HLB), mixed-mode cation-exchange (MCX and X-C), and mixed-mode weak cation-exchange (WCX), with different corresponding elution solvents. The samples were analysed using LC-MS/MS, with a phenyl column (150 × 4.6 mm, 2.5 μm). The best extraction recoveries (≥92.3%) of all analytes were obtained with the C8 phase, using methanol as the elution solvent. The optimised method was validated in the clinically relevant ranges, showing adequate precision (inter-day RSD ≤ 14.3%) and accuracy (inter-day bias −12.7–13.5%). Finally, its applicability was successfully proven by the analysis of samples from breast cancer patients. |
format | Online Article Text |
id | pubmed-10610126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106101262023-10-28 Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples Turković, Lu Mutavdžić Pavlović, Dragana Mlinarić, Zvonimir Skenderović, Anamarija Silovski, Tajana Sertić, Miranda Pharmaceuticals (Basel) Article In the development of bioanalytical LC-MS methods for the determination of drugs in plasma samples in a clinical setting, adequate sample preparation is of utmost importance. The main goals are to achieve the selective extraction of the analytes of interest and attain thorough matrix removal while retaining acceptable ecological properties, cost-effectiveness, and high throughput. Solid-phase extraction (SPE) offers a versatile range of options, from the selection of an appropriate sorbent to the optimisation of the washing and elution conditions. In this work, the first SPE method for the simultaneous extraction of six anticancer drugs used in novel therapeutic combinations for advanced breast cancer treatment—palbociclib, ribociclib, abemaciclib, anastrozole, letrozole, and fulvestrant—was developed. The following sorbent chemistries were tested: octylsilyl (C8), octadecylsilyl (C18), hydrophilic–lipophilic balance (HLB), mixed-mode cation-exchange (MCX and X-C), and mixed-mode weak cation-exchange (WCX), with different corresponding elution solvents. The samples were analysed using LC-MS/MS, with a phenyl column (150 × 4.6 mm, 2.5 μm). The best extraction recoveries (≥92.3%) of all analytes were obtained with the C8 phase, using methanol as the elution solvent. The optimised method was validated in the clinically relevant ranges, showing adequate precision (inter-day RSD ≤ 14.3%) and accuracy (inter-day bias −12.7–13.5%). Finally, its applicability was successfully proven by the analysis of samples from breast cancer patients. MDPI 2023-10-12 /pmc/articles/PMC10610126/ /pubmed/37895916 http://dx.doi.org/10.3390/ph16101445 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Turković, Lu Mutavdžić Pavlović, Dragana Mlinarić, Zvonimir Skenderović, Anamarija Silovski, Tajana Sertić, Miranda Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples |
title | Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples |
title_full | Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples |
title_fullStr | Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples |
title_full_unstemmed | Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples |
title_short | Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples |
title_sort | optimisation of solid-phase extraction and lc-ms/ms analysis of six breast cancer drugs in patient plasma samples |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610126/ https://www.ncbi.nlm.nih.gov/pubmed/37895916 http://dx.doi.org/10.3390/ph16101445 |
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