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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...

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Autores principales: Turković, Lu, Mutavdžić Pavlović, Dragana, Mlinarić, Zvonimir, Skenderović, Anamarija, Silovski, Tajana, Sertić, Miranda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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