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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MDPI AG
2023-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1445 |
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| author | Lu Turković Dragana Mutavdžić Pavlović Zvonimir Mlinarić Anamarija Skenderović Tajana Silovski Miranda Sertić |
| author_facet | Lu Turković Dragana Mutavdžić Pavlović Zvonimir Mlinarić Anamarija Skenderović Tajana Silovski Miranda Sertić |
| author_sort | Lu Turković |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T20:58:29Z |
| format | Article |
| id | doaj.art-33f64e0732434da3a3ae9d2477aabf9a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:58:29Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-33f64e0732434da3a3ae9d2477aabf9a2023-11-19T17:42:37ZengMDPI AGPharmaceuticals1424-82472023-10-011610144510.3390/ph16101445Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma SamplesLu Turković0Dragana Mutavdžić Pavlović1Zvonimir Mlinarić2Anamarija Skenderović3Tajana Silovski4Miranda Sertić5Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, CroatiaDepartment of Analytical Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulicev trg 20, 10000 Zagreb, CroatiaDepartment of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, CroatiaGxR&D Analytics Zagreb, Global R&D, Teva Pharmaceuticals, Prilaz Baruna Filipovica 25, 10000 Zagreb, CroatiaDepartment of Oncology, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, CroatiaDepartment of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, CroatiaIn 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.https://www.mdpi.com/1424-8247/16/10/1445solid-phase extractionbreast cancerCDK4/6 inhibitorstherapeutic drug monitoringliquid chromatographymass spectrometry |
| spellingShingle | Lu Turković Dragana Mutavdžić Pavlović Zvonimir Mlinarić Anamarija Skenderović Tajana Silovski Miranda Sertić Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples Pharmaceuticals solid-phase extraction breast cancer CDK4/6 inhibitors therapeutic drug monitoring liquid chromatography mass spectrometry |
| 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 | solid-phase extraction breast cancer CDK4/6 inhibitors therapeutic drug monitoring liquid chromatography mass spectrometry |
| url | https://www.mdpi.com/1424-8247/16/10/1445 |
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