Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay
Abstract Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive...
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| Format: | Article |
| Language: | English |
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BMC
2017-11-01
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| Series: | Chemistry Central Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s13065-017-0353-6 |
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| author | Xiao-Yang Zhou Ling-Jing Yuan Zhe Chen Peng-Fei Tang Xiang-Yu Li Guo-Xin Hu Jian-Ping Cai |
| author_facet | Xiao-Yang Zhou Ling-Jing Yuan Zhe Chen Peng-Fei Tang Xiang-Yu Li Guo-Xin Hu Jian-Ping Cai |
| author_sort | Xiao-Yang Zhou |
| collection | DOAJ |
| description | Abstract Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive and specific ultra high-performance liquid chromatography with tandem mass spectrometry assay was established and verified for the determination of lesinurad in rat plasma and was described in details for the first time. Chromatographic separation of lesinurad and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18 column (3.0 × 100 mm, 1.8 µm) using methanol–water (70:30, v/v) as the mobile phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out using an electrospray ionization source in positive mode. Multiple reaction monitoring was used for quantification of the precursor to product ion at m/z 405.6 → 220.9 for lesinurad and m/z 285.1 → 192.8 for IS. The assay was well validated for selectivity, accuracy, precision, recovery, linearity, matrix effects, and stability. The verified method was applied to obtain the pharmacokinetic parameters and concentration–time profiles for lesinurad after oral/intravenous administration in rats. The study might provide an important reference and a necessary complement for the qualitative and quantitative evaluation of lesinurad. |
| first_indexed | 2024-12-16T09:44:14Z |
| format | Article |
| id | doaj.art-4a8358317a434bedaa3a94bd723ab404 |
| institution | Directory Open Access Journal |
| issn | 1752-153X |
| language | English |
| last_indexed | 2024-12-16T09:44:14Z |
| publishDate | 2017-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Chemistry Central Journal |
| spelling | doaj.art-4a8358317a434bedaa3a94bd723ab4042022-12-21T22:36:13ZengBMCChemistry Central Journal1752-153X2017-11-011111710.1186/s13065-017-0353-6Determination of lesinurad in rat plasma by a UHPLC–MS/MS assayXiao-Yang Zhou0Ling-Jing Yuan1Zhe Chen2Peng-Fei Tang3Xiang-Yu Li4Guo-Xin Hu5Jian-Ping Cai6The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of GerontologyDepartment of Pharmacology, School of Pharmacy, Wenzhou Medical UniversityDepartment of Pharmacology, School of Pharmacy, Wenzhou Medical UniversityDepartment of Pharmacology, School of Pharmacy, Wenzhou Medical UniversityDepartment of Pharmacology, School of Pharmacy, Wenzhou Medical UniversityDepartment of Pharmacology, School of Pharmacy, Wenzhou Medical UniversityThe MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of GerontologyAbstract Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive and specific ultra high-performance liquid chromatography with tandem mass spectrometry assay was established and verified for the determination of lesinurad in rat plasma and was described in details for the first time. Chromatographic separation of lesinurad and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18 column (3.0 × 100 mm, 1.8 µm) using methanol–water (70:30, v/v) as the mobile phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out using an electrospray ionization source in positive mode. Multiple reaction monitoring was used for quantification of the precursor to product ion at m/z 405.6 → 220.9 for lesinurad and m/z 285.1 → 192.8 for IS. The assay was well validated for selectivity, accuracy, precision, recovery, linearity, matrix effects, and stability. The verified method was applied to obtain the pharmacokinetic parameters and concentration–time profiles for lesinurad after oral/intravenous administration in rats. The study might provide an important reference and a necessary complement for the qualitative and quantitative evaluation of lesinurad.http://link.springer.com/article/10.1186/s13065-017-0353-6LesinuradUHPLC–MS/MSRat plasmaPharmacokinetics |
| spellingShingle | Xiao-Yang Zhou Ling-Jing Yuan Zhe Chen Peng-Fei Tang Xiang-Yu Li Guo-Xin Hu Jian-Ping Cai Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay Chemistry Central Journal Lesinurad UHPLC–MS/MS Rat plasma Pharmacokinetics |
| title | Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay |
| title_full | Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay |
| title_fullStr | Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay |
| title_full_unstemmed | Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay |
| title_short | Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay |
| title_sort | determination of lesinurad in rat plasma by a uhplc ms ms assay |
| topic | Lesinurad UHPLC–MS/MS Rat plasma Pharmacokinetics |
| url | http://link.springer.com/article/10.1186/s13065-017-0353-6 |
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