Article ; Online: UPLC-MS/MS for the Herb-Drug Interactions of Xiao-Ai-Ping Injection on Enasidenib in Rats Based on Pharmacokinetics.
2021 Volume 2021, Page(s) 6636266
Abstract: Objective: To develop and validate a sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of enasidenib in rat plasma and to investigate the effect of Xiao-ai-ping injection (XAPI) ...
| Abstract | Objective: To develop and validate a sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of enasidenib in rat plasma and to investigate the effect of Xiao-ai-ping injection (XAPI) on the pharmacokinetics of enasidenib in rats. Methods: The rat plasma was precipitated with acetonitrile, enasidenib and internal standard (IS) were separated on an Acquity UPLC BEH C18 column, and acetonitrile and 0.1% formic acid were used as the mobile phase in gradient mode. Enasidenib and IS were monitored and detected by multiple reaction monitoring (MRM) using tandem mass spectrometry in positive ion mode. 12 Sprague-Dawley (SD) rats were randomly divided into control group (group A) and experimental group (group B), 6 rats in each group. Group B was intramuscularly injected with XAPI (0.3 mL/kg) every morning, 7 days in a row. Group A was intramuscularly injected with normal saline, 7 days in a row. On the seventh day, enasidenib (10 mg/kg) was given to both groups 30 min after injection of normal saline (group A) or XAPI (group B), and the blood was collected at different time points such as 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 h. The concentration of enasidenib was detected by UPLC-MS/MS, and the main parameters of pharmacokinetic of enasidenib were calculated using the DAS 2.0 software. Results: Under the current experimental conditions, this UPLC method showed good linearity in the detection of enasidenib. Interday and intraday precision did not exceed 10%, the range of accuracy values were from -1.43% to 2.76%. The results of matrix effect, extraction recovery, and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The Conclusion: An UPLC-MS/MS method for the determination of enasidenib in rat plasma was established. XAPI can inhibit the metabolism of enasidenib and increase the concentration of enasidenib in rats. It is suggested that when XAPI was combined with enasidenib, the herb-drug interaction and adverse reactions should be paid attention to, and the dosage should be adjusted if necessary. |
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| MeSH term(s) | Aminopyridines/pharmacokinetics ; Aminopyridines/pharmacology ; Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacokinetics ; Drugs, Chinese Herbal/pharmacology ; Herb-Drug Interactions ; Male ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Triazines/pharmacokinetics ; Triazines/pharmacology |
| Chemical Substances | Aminopyridines ; Drugs, Chinese Herbal ; Marsdeniae tenacissimae extract ; Triazines ; enasidenib (3T1SS4E7AG) |
| Language | English |
| Publishing date | 2021-02-23 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2698540-8 |
| ISSN | 2314-6141 ; 2314-6133 |
| ISSN (online) | 2314-6141 |
| ISSN | 2314-6133 |
| DOI | 10.1155/2021/6636266 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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