Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine
Context Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure.Objective For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assa...
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Taylor & Francis Group
2024-12-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2024.2425648 |
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| author | Dongxin Chen Jie Chen Yuxin Shen Xiaohai Chen Hailun Xia Ya-nan Liu Ren-ai Xu |
| author_facet | Dongxin Chen Jie Chen Yuxin Shen Xiaohai Chen Hailun Xia Ya-nan Liu Ren-ai Xu |
| author_sort | Dongxin Chen |
| collection | DOAJ |
| description | Context Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure.Objective For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine in vivo and in vitro was researched.Materials and methods Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of m/z 526.01 → 72.04 for almonertinib, m/z 512.18 → 455.08 for HAS-719 and m/z 447.16 → 128.11 for IS, respectively.Results There was favourable linearity in the 0.5–200 ng/mL calibration range for almonertinib and 0.5–100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine in vivo and in vitro. The half-maximal inhibitory concentration (IC50) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC(0-∞), AUC(0-t) and Cmax, but had no effect on the metabolism of HAS-719.Conclusion According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib in vitro and in vivo. |
| format | Article |
| id | doaj-art-1a2e8cd8b4c44c0384c3efa5674d718c |
| institution | Kabale University |
| issn | 1388-0209 1744-5116 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Pharmaceutical Biology |
| spelling | doaj-art-1a2e8cd8b4c44c0384c3efa5674d718c2024-12-09T07:41:45ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162024-12-0162187488110.1080/13880209.2024.2425648Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipineDongxin Chen0Jie Chen1Yuxin Shen2Xiaohai Chen3Hailun Xia4Ya-nan Liu5Ren-ai Xu6The Affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaContext Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure.Objective For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine in vivo and in vitro was researched.Materials and methods Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of m/z 526.01 → 72.04 for almonertinib, m/z 512.18 → 455.08 for HAS-719 and m/z 447.16 → 128.11 for IS, respectively.Results There was favourable linearity in the 0.5–200 ng/mL calibration range for almonertinib and 0.5–100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine in vivo and in vitro. The half-maximal inhibitory concentration (IC50) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC(0-∞), AUC(0-t) and Cmax, but had no effect on the metabolism of HAS-719.Conclusion According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib in vitro and in vivo.https://www.tandfonline.com/doi/10.1080/13880209.2024.2425648AlmonertinibHAS-719nicardipineUPLC-MS/MSrat plasma |
| spellingShingle | Dongxin Chen Jie Chen Yuxin Shen Xiaohai Chen Hailun Xia Ya-nan Liu Ren-ai Xu Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine Pharmaceutical Biology Almonertinib HAS-719 nicardipine UPLC-MS/MS rat plasma |
| title | Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine |
| title_full | Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine |
| title_fullStr | Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine |
| title_full_unstemmed | Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine |
| title_short | Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine |
| title_sort | optimization of a sensitive and reliable uplc ms ms method to simultaneously quantify almonertinib and has 719 and its application to study the interaction with nicardipine |
| topic | Almonertinib HAS-719 nicardipine UPLC-MS/MS rat plasma |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2024.2425648 |
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