Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics
The primary objective of this study was to develop and validate an efficient and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach as a means to detect tropifexor plasma concentrations in beagle dogs and to study its pharmacokinetic profile in beagle dog...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Analytical Methods in Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2022/2823214 |
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| author | Yan-Ding Su Xin-Yi Wei Xiao-Hang Su Ghulam Woshur Xiao-Nan Geng Xiang-Jun Qiu |
| author_facet | Yan-Ding Su Xin-Yi Wei Xiao-Hang Su Ghulam Woshur Xiao-Nan Geng Xiang-Jun Qiu |
| author_sort | Yan-Ding Su |
| collection | DOAJ |
| description | The primary objective of this study was to develop and validate an efficient and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach as a means to detect tropifexor plasma concentrations in beagle dogs and to study its pharmacokinetic profile in beagle dogs. The chromatographic separation of tropifexor and oprozomib (internal standard, ISTD) on the column, with the addition of acetonitrile for rapid precipitation and protein extraction, was achieved with 0.1% formic acid aqueous solution-acetonitrile for the mobile phase. A Xevo TQ-S triple quadrupole tandem mass spectrometer, under the selective reaction monitoring (SRM) mode, for the determination of the concentrations in the positive ion mode. The mass transfer pairs of tropifexor and oprozomib (ISTD) were m/z 604.08 ⟶ 228.03 and m/z 533.18 ⟶ 199.01, respectively. The profile displayed well linearity with calibration curves for tropifexor and oprozomib (ISTD) ranging from 1.0 to 200 ng/mL. In parallel, the lower limit of quantification (LLOQ) value for tropifexor could be measured with the aid of this novel technique at 1.0 ng/mL. In addition, the scope of intraday and interday for analyte accuracy was between −4.86% and 1.16%, with a precision of <7.31%. The recoveries of the analytes were >88.13% and were free of significant matrix effects. The stability met the requirements for the quantification of plasma samples under various conditions. Finally, the pharmacokinetic profile of tropifexor in beagle dog plasma following oral administration of 0.33 mg/kg tropifexor was determined by using the method facilitated in this work. |
| format | Article |
| id | doaj-art-327210def36a46348ec480362f2a7d33 |
| institution | Kabale University |
| issn | 2090-8873 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Analytical Methods in Chemistry |
| spelling | doaj-art-327210def36a46348ec480362f2a7d332025-02-03T05:49:21ZengWileyJournal of Analytical Methods in Chemistry2090-88732022-01-01202210.1155/2022/2823214Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in PharmacokineticsYan-Ding Su0Xin-Yi Wei1Xiao-Hang Su2Ghulam Woshur3Xiao-Nan Geng4Xiang-Jun Qiu5School of Basic Medical SciencesSchool of Basic Medical SciencesSchool of Basic Medical SciencesSchool of Basic Medical SciencesSchool of Basic Medical SciencesSchool of Basic Medical SciencesThe primary objective of this study was to develop and validate an efficient and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach as a means to detect tropifexor plasma concentrations in beagle dogs and to study its pharmacokinetic profile in beagle dogs. The chromatographic separation of tropifexor and oprozomib (internal standard, ISTD) on the column, with the addition of acetonitrile for rapid precipitation and protein extraction, was achieved with 0.1% formic acid aqueous solution-acetonitrile for the mobile phase. A Xevo TQ-S triple quadrupole tandem mass spectrometer, under the selective reaction monitoring (SRM) mode, for the determination of the concentrations in the positive ion mode. The mass transfer pairs of tropifexor and oprozomib (ISTD) were m/z 604.08 ⟶ 228.03 and m/z 533.18 ⟶ 199.01, respectively. The profile displayed well linearity with calibration curves for tropifexor and oprozomib (ISTD) ranging from 1.0 to 200 ng/mL. In parallel, the lower limit of quantification (LLOQ) value for tropifexor could be measured with the aid of this novel technique at 1.0 ng/mL. In addition, the scope of intraday and interday for analyte accuracy was between −4.86% and 1.16%, with a precision of <7.31%. The recoveries of the analytes were >88.13% and were free of significant matrix effects. The stability met the requirements for the quantification of plasma samples under various conditions. Finally, the pharmacokinetic profile of tropifexor in beagle dog plasma following oral administration of 0.33 mg/kg tropifexor was determined by using the method facilitated in this work.http://dx.doi.org/10.1155/2022/2823214 |
| spellingShingle | Yan-Ding Su Xin-Yi Wei Xiao-Hang Su Ghulam Woshur Xiao-Nan Geng Xiang-Jun Qiu Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics Journal of Analytical Methods in Chemistry |
| title | Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics |
| title_full | Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics |
| title_fullStr | Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics |
| title_full_unstemmed | Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics |
| title_short | Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics |
| title_sort | determination of tropifexor in beagle dog plasma by uplc ms ms and its application in pharmacokinetics |
| url | http://dx.doi.org/10.1155/2022/2823214 |
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