Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy
The antihyerlipidemic drug atorvastatin (ATR) is used worldwide as part of the strategy to prevent cardiovascular events. The high prevalence of patient nonadherence remains an important challenge which could be addressed efficiently by precision pharmacotherapy based on therapeutic drug monitoring...
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MDPI AG
2021-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/5/1324 |
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| author | Gellért Balázs Karvaly István Vincze István Karádi Barna Vásárhelyi András Zsáry |
| author_facet | Gellért Balázs Karvaly István Vincze István Karádi Barna Vásárhelyi András Zsáry |
| author_sort | Gellért Balázs Karvaly |
| collection | DOAJ |
| description | The antihyerlipidemic drug atorvastatin (ATR) is used worldwide as part of the strategy to prevent cardiovascular events. The high prevalence of patient nonadherence remains an important challenge which could be addressed efficiently by precision pharmacotherapy based on therapeutic drug monitoring (TDM). ATR is metabolized to pharmacologically active metabolites, and evidence shows that the sums of ATR acid and lactone form concentrations (ATR + ATRL), or of ATR and hydroxylated metabolites (ATR + MET) should be assayed. A method is presented for the analysis of these substances in serum. Method validation included the estimation of the quantitative relationship between the concentrations and the standard deviations (SD), which supports the optimal incorporation of TDM results into nonparametric pharmacokinetic models. The concentrations of the analytes were evaluated in human subjects receiving ATR. The method’s performance improved by taking the sums of acid and lactone concentrations into account. The concentration–SD relationship was linear, and we recommend applying Theil’s regression for estimating the assay error. All analytes could be detected by 2 h post dose in the samples of human subjects. The changes in metabolite/parent drug concentration ratios in time depended on the dose. The method is suitable for the TDM of ATR with a focus on precision pharmacotherapy. |
| first_indexed | 2024-03-09T06:00:42Z |
| format | Article |
| id | doaj.art-e7296b31d34a4700938496ca7e86112c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T06:00:42Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e7296b31d34a4700938496ca7e86112c2023-12-03T12:09:26ZengMDPI AGMolecules1420-30492021-03-01265132410.3390/molecules26051324Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision PharmacotherapyGellért Balázs Karvaly0István Vincze1István Karádi2Barna Vásárhelyi3András Zsáry4Department of Laboratory Medicine, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, HungaryDepartment of Laboratory Medicine, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, HungaryDepartment of Internal Medicine and Hematology, Semmelweis University, Szentkirályi út 46, H-1088 Budapest, HungaryDepartment of Laboratory Medicine, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, HungaryDepartment of Internal Medicine and Hematology, Semmelweis University, Szentkirályi út 46, H-1088 Budapest, HungaryThe antihyerlipidemic drug atorvastatin (ATR) is used worldwide as part of the strategy to prevent cardiovascular events. The high prevalence of patient nonadherence remains an important challenge which could be addressed efficiently by precision pharmacotherapy based on therapeutic drug monitoring (TDM). ATR is metabolized to pharmacologically active metabolites, and evidence shows that the sums of ATR acid and lactone form concentrations (ATR + ATRL), or of ATR and hydroxylated metabolites (ATR + MET) should be assayed. A method is presented for the analysis of these substances in serum. Method validation included the estimation of the quantitative relationship between the concentrations and the standard deviations (SD), which supports the optimal incorporation of TDM results into nonparametric pharmacokinetic models. The concentrations of the analytes were evaluated in human subjects receiving ATR. The method’s performance improved by taking the sums of acid and lactone concentrations into account. The concentration–SD relationship was linear, and we recommend applying Theil’s regression for estimating the assay error. All analytes could be detected by 2 h post dose in the samples of human subjects. The changes in metabolite/parent drug concentration ratios in time depended on the dose. The method is suitable for the TDM of ATR with a focus on precision pharmacotherapy.https://www.mdpi.com/1420-3049/26/5/1324atorvastatinhydroxyatorvastatinatorvastatin lactonetherapeutic drug monitoringpharmacokineticsindividualized drug therapy |
| spellingShingle | Gellért Balázs Karvaly István Vincze István Karádi Barna Vásárhelyi András Zsáry Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy Molecules atorvastatin hydroxyatorvastatin atorvastatin lactone therapeutic drug monitoring pharmacokinetics individualized drug therapy |
| title | Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy |
| title_full | Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy |
| title_fullStr | Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy |
| title_full_unstemmed | Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy |
| title_short | Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy |
| title_sort | sensitive high throughput liquid chromatography tandem mass spectrometry analysis of atorvastatin and its pharmacologically active metabolites in serum for supporting precision pharmacotherapy |
| topic | atorvastatin hydroxyatorvastatin atorvastatin lactone therapeutic drug monitoring pharmacokinetics individualized drug therapy |
| url | https://www.mdpi.com/1420-3049/26/5/1324 |
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