Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in rats
Abstract We established a method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC‒MS/MS) to quantitatively measure tepotinib, which was validated as acceptable and used in the evaluation of food-drug interactions between tepotinib and naringenin in rats. We used pemiga...
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2024-11-01
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| Online Access: | https://doi.org/10.1186/s13065-024-01293-1 |
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| author | Zhe Chen Chaojie Chen Ya-nan Liu Xinhao Xu Shunbin Luo |
| author_facet | Zhe Chen Chaojie Chen Ya-nan Liu Xinhao Xu Shunbin Luo |
| author_sort | Zhe Chen |
| collection | DOAJ |
| description | Abstract We established a method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC‒MS/MS) to quantitatively measure tepotinib, which was validated as acceptable and used in the evaluation of food-drug interactions between tepotinib and naringenin in rats. We used pemigatinib as the internal standard (IS), and acetonitrile and 0.1% formic acid aqueous solution constituted the mobile phase. To extract the target analyte, acetonitrile was used for protein precipitation (PPT). For UPLC‒MS/MS, we performed liquid chromatography using a C18 column, and mass spectrometry was performed in positive multiple reaction monitoring (MRM) mode. Excellent linearity was shown in the range of 0.1–500 ng/mL, and the coefficient of correlation was > 0.99. Notably, the lower limit of quantification (LLOQ) for tepotinib was determined to be 0.1 ng/mL. The intra- and inter-day accuracy of tepotinib ranged from − 1.7 to 7.3%, while the precision was ≤ 8.4%, at three concentrations except LLOQ. The recovery of each substance was ≥ 81.2%, and the matrix effects were within 90.5-98.6%. The stabilities of all analytes under different conditions met all requirements for quantitation in plasma samples. The relevant parameters, such as LLOQ, were evaluated in accordance with the principles of the Food and Drug Administration (FDA) biological verification method. Food-drug interaction study had shown that the plasma concentration of tepotinib could be significantly increased, accompanied by a decrease in clearance rate when administered with 50 mg/kg naringenin. The results showed that naringenin could increase the plasma concentration and decrease the clearance rate of tepotinib when naringenin and tepotinib were administered at the same time. |
| format | Article |
| id | doaj-art-01ac677fb8b84b36ace4047b7ba50bea |
| institution | DOAJ |
| issn | 2661-801X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | BMC Chemistry |
| spelling | doaj-art-01ac677fb8b84b36ace4047b7ba50bea2025-08-20T02:50:00ZengBMCBMC Chemistry2661-801X2024-11-011811810.1186/s13065-024-01293-1Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in ratsZhe Chen0Chaojie Chen1Ya-nan Liu2Xinhao Xu3Shunbin Luo4The Third Affiliated Hospital of Shanghai University (Wenzhou People’s Hospital)The First Affiliated Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Wenzhou Medical UniversityThe People’s Hospital of LishuiAbstract We established a method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC‒MS/MS) to quantitatively measure tepotinib, which was validated as acceptable and used in the evaluation of food-drug interactions between tepotinib and naringenin in rats. We used pemigatinib as the internal standard (IS), and acetonitrile and 0.1% formic acid aqueous solution constituted the mobile phase. To extract the target analyte, acetonitrile was used for protein precipitation (PPT). For UPLC‒MS/MS, we performed liquid chromatography using a C18 column, and mass spectrometry was performed in positive multiple reaction monitoring (MRM) mode. Excellent linearity was shown in the range of 0.1–500 ng/mL, and the coefficient of correlation was > 0.99. Notably, the lower limit of quantification (LLOQ) for tepotinib was determined to be 0.1 ng/mL. The intra- and inter-day accuracy of tepotinib ranged from − 1.7 to 7.3%, while the precision was ≤ 8.4%, at three concentrations except LLOQ. The recovery of each substance was ≥ 81.2%, and the matrix effects were within 90.5-98.6%. The stabilities of all analytes under different conditions met all requirements for quantitation in plasma samples. The relevant parameters, such as LLOQ, were evaluated in accordance with the principles of the Food and Drug Administration (FDA) biological verification method. Food-drug interaction study had shown that the plasma concentration of tepotinib could be significantly increased, accompanied by a decrease in clearance rate when administered with 50 mg/kg naringenin. The results showed that naringenin could increase the plasma concentration and decrease the clearance rate of tepotinib when naringenin and tepotinib were administered at the same time.https://doi.org/10.1186/s13065-024-01293-1TepotinibPharmacokineticsNaringeninDrug‒drug interactionUPLC‒MS/MS |
| spellingShingle | Zhe Chen Chaojie Chen Ya-nan Liu Xinhao Xu Shunbin Luo Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in rats BMC Chemistry Tepotinib Pharmacokinetics Naringenin Drug‒drug interaction UPLC‒MS/MS |
| title | Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in rats |
| title_full | Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in rats |
| title_fullStr | Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in rats |
| title_full_unstemmed | Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in rats |
| title_short | Measurement of tepotinib by UPLC‒MS/MS and its interaction with naringenin in rats |
| title_sort | measurement of tepotinib by uplc ms ms and its interaction with naringenin in rats |
| topic | Tepotinib Pharmacokinetics Naringenin Drug‒drug interaction UPLC‒MS/MS |
| url | https://doi.org/10.1186/s13065-024-01293-1 |
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