An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib
Osimertinib is a novel oral, potent, and irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treatment of advanced T790M mutation-positive advanced non-small cell lung cancer, which is commonly combined with ginsenoside Rg3 in clinic to enhance the efficacy and min...
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| Format: | Article |
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2020-01-01
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| Series: | International Journal of Analytical Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2020/8814214 |
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| author | Zhenzhen Ying Jingyao Wei Ruijuan Liu Fang Zhao Yifang Yu Xin Tian |
| author_facet | Zhenzhen Ying Jingyao Wei Ruijuan Liu Fang Zhao Yifang Yu Xin Tian |
| author_sort | Zhenzhen Ying |
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| description | Osimertinib is a novel oral, potent, and irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treatment of advanced T790M mutation-positive advanced non-small cell lung cancer, which is commonly combined with ginsenoside Rg3 in clinic to enhance the efficacy and minimize adverse reactions. In the present study, a highly sensitive UPLC-MS/MS method was established and validated for analysis of osimertinib in rat plasma according to US FDA guideline. Separation was performed on a C18 (2.1 × 50 mm, 2.6 μm) column using a gradient elution of ammonium formate (10 mM) with 0.1% formic acid buffer (A) and ACN (B) at a flow rate of 0.2 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization in the MRM mode. The method was validated over a concentration range of 1–400 ng/mL for osimertinib. The intra- and interday accuracy and precision values were within ±15%. No significant degradation occurred under the experimental conditions in stability assays. There was a further investigation on the effects of multiple doses of ginsenoside Rg3 on the pharmacokinetics of osimertinib in rats for the first time. The results implied that osimertinib exhibited a slow absorption and moderate-rate elimination in rats following oral administration. Coadministeration with ginsenoside Rg3 (5 mg/kg, 7 days, i.g.) may have no effect on the pharmacokinetics of osimertinib in rats. The results provide a reference for the clinical concomitant medications of Rg3 and osimertinib. |
| format | Article |
| id | doaj-art-aec7a7f0cf3a451bbdc9f3137286ce5a |
| institution | Kabale University |
| issn | 1687-8760 1687-8779 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Analytical Chemistry |
| spelling | doaj-art-aec7a7f0cf3a451bbdc9f3137286ce5a2025-02-03T01:07:57ZengWileyInternational Journal of Analytical Chemistry1687-87601687-87792020-01-01202010.1155/2020/88142148814214An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of OsimertinibZhenzhen Ying0Jingyao Wei1Ruijuan Liu2Fang Zhao3Yifang Yu4Xin Tian5Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaOsimertinib is a novel oral, potent, and irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treatment of advanced T790M mutation-positive advanced non-small cell lung cancer, which is commonly combined with ginsenoside Rg3 in clinic to enhance the efficacy and minimize adverse reactions. In the present study, a highly sensitive UPLC-MS/MS method was established and validated for analysis of osimertinib in rat plasma according to US FDA guideline. Separation was performed on a C18 (2.1 × 50 mm, 2.6 μm) column using a gradient elution of ammonium formate (10 mM) with 0.1% formic acid buffer (A) and ACN (B) at a flow rate of 0.2 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization in the MRM mode. The method was validated over a concentration range of 1–400 ng/mL for osimertinib. The intra- and interday accuracy and precision values were within ±15%. No significant degradation occurred under the experimental conditions in stability assays. There was a further investigation on the effects of multiple doses of ginsenoside Rg3 on the pharmacokinetics of osimertinib in rats for the first time. The results implied that osimertinib exhibited a slow absorption and moderate-rate elimination in rats following oral administration. Coadministeration with ginsenoside Rg3 (5 mg/kg, 7 days, i.g.) may have no effect on the pharmacokinetics of osimertinib in rats. The results provide a reference for the clinical concomitant medications of Rg3 and osimertinib.http://dx.doi.org/10.1155/2020/8814214 |
| spellingShingle | Zhenzhen Ying Jingyao Wei Ruijuan Liu Fang Zhao Yifang Yu Xin Tian An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib International Journal of Analytical Chemistry |
| title | An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib |
| title_full | An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib |
| title_fullStr | An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib |
| title_full_unstemmed | An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib |
| title_short | An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib |
| title_sort | uplc ms ms method for determination of osimertinib in rat plasma application to investigating the effect of ginsenoside rg3 on the pharmacokinetics of osimertinib |
| url | http://dx.doi.org/10.1155/2020/8814214 |
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