A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma
Oprozomib, as a second-generation orally bioavailable protease inhibitor (PI), is undergoing clinical evaluation for the treatment of haematological malignancies. In relapsed refractory multiple myeloma (RRMM) patients, oprozomib has shown good efficacy as a single agent or combination therapy. In t...
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Wiley
2023-01-01
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| Series: | Journal of Analytical Methods in Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2023/3678599 |
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| author | Xia Li Ya-nan Liu En Zhang Ren-ai Xu Tingyong Yang Shunbin Luo |
| author_facet | Xia Li Ya-nan Liu En Zhang Ren-ai Xu Tingyong Yang Shunbin Luo |
| author_sort | Xia Li |
| collection | DOAJ |
| description | Oprozomib, as a second-generation orally bioavailable protease inhibitor (PI), is undergoing clinical evaluation for the treatment of haematological malignancies. In relapsed refractory multiple myeloma (RRMM) patients, oprozomib has shown good efficacy as a single agent or combination therapy. In this experiment, our purpose was to validate a sensitive and rapid method for the determination of oprozomib concentration in rat plasma by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The samples were treated with acetonitrile as the precipitant and separated by gradient elution using a Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm). Using the selective reaction monitoring (SRM) method, the measurement was finished with the ion transitions of m/z 533.18 ⟶ 199.01 for oprozomib and m/z 493.03 ⟶ 112.03 for tepotinib (internal standard, IS), respectively. Meanwhile, acetonitrile and 0.1% formic acid aqueous solution were used as the mobile phase, and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) of the method was 1.0 ng/mL, and the linear relationship was good in the range of 1.0–100 ng/mL. In addition, the precision of four concentration levels was determined with the values of 3.1–7.3% and the accuracy was from −14.9% to 12.9%. Moreover, the recovery was determined to be from 85.1% to 96.1%, and the values of matrix effect were no more than 110.4%. The optimized UPLC-MS/MS method was also suitable for the pharmacokinetic study of rats after a single oral administration of 21 mg/kg oprozomib. |
| format | Article |
| id | doaj-art-e7611237082b4e1ba1ad4906cc36c212 |
| institution | OA Journals |
| issn | 2090-8873 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Analytical Methods in Chemistry |
| spelling | doaj-art-e7611237082b4e1ba1ad4906cc36c2122025-08-20T02:21:09ZengWileyJournal of Analytical Methods in Chemistry2090-88732023-01-01202310.1155/2023/3678599A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat PlasmaXia Li0Ya-nan Liu1En Zhang2Ren-ai Xu3Tingyong Yang4Shunbin Luo5Clinical LaboratoryThe First Affiliated Hospital of Wenzhou Medical UniversityClinical LaboratoryThe First Affiliated Hospital of Wenzhou Medical UniversityChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentThe People’s Hospital of LishuiOprozomib, as a second-generation orally bioavailable protease inhibitor (PI), is undergoing clinical evaluation for the treatment of haematological malignancies. In relapsed refractory multiple myeloma (RRMM) patients, oprozomib has shown good efficacy as a single agent or combination therapy. In this experiment, our purpose was to validate a sensitive and rapid method for the determination of oprozomib concentration in rat plasma by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The samples were treated with acetonitrile as the precipitant and separated by gradient elution using a Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm). Using the selective reaction monitoring (SRM) method, the measurement was finished with the ion transitions of m/z 533.18 ⟶ 199.01 for oprozomib and m/z 493.03 ⟶ 112.03 for tepotinib (internal standard, IS), respectively. Meanwhile, acetonitrile and 0.1% formic acid aqueous solution were used as the mobile phase, and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) of the method was 1.0 ng/mL, and the linear relationship was good in the range of 1.0–100 ng/mL. In addition, the precision of four concentration levels was determined with the values of 3.1–7.3% and the accuracy was from −14.9% to 12.9%. Moreover, the recovery was determined to be from 85.1% to 96.1%, and the values of matrix effect were no more than 110.4%. The optimized UPLC-MS/MS method was also suitable for the pharmacokinetic study of rats after a single oral administration of 21 mg/kg oprozomib.http://dx.doi.org/10.1155/2023/3678599 |
| spellingShingle | Xia Li Ya-nan Liu En Zhang Ren-ai Xu Tingyong Yang Shunbin Luo A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma Journal of Analytical Methods in Chemistry |
| title | A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma |
| title_full | A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma |
| title_fullStr | A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma |
| title_full_unstemmed | A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma |
| title_short | A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma |
| title_sort | reliable and effective uplc ms ms method for the determination of oprozomib in rat plasma |
| url | http://dx.doi.org/10.1155/2023/3678599 |
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