Validated LC-MS/MS Method for Simultaneous Quantitation of Enasidenib and its Active Metabolite, AGI-16903 in Small Volume Mice Plasma: Application to a Pharmacokinetic Study
| Autor: | Sreekanth Dittakavi, Vinay Kiran, Ashok Zakkula, Ramesh Mullangi, Buchi Reddy Purra, Gurulingappa Hallur |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Resolution (mass spectrometry) Formic acid Administration Oral Aminopyridines Antineoplastic Agents Enasidenib 01 natural sciences Sensitivity and Specificity 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Column chromatography Pharmacokinetics Drug Stability Tandem Mass Spectrometry Drug Discovery Protein precipitation Animals Humans Acetonitrile Active metabolite Chromatography High Pressure Liquid Chromatography 010405 organic chemistry Chemistry Triazines Reproducibility of Results General Medicine Reference Standards 0104 chemical sciences Leukemia Myeloid Acute 030220 oncology & carcinogenesis Calibration Models Animal |
| Zdroj: | Drug research. 70(1) |
| ISSN: | 2194-9387 |
| Popis: | Enasidenib is a selective mutant isocitrate dehydrogenase 2 inhibitor approved for the treatment of relapsed and refractory acute myeloid leukemia patients. A sensitive and rapid method has been developed and validated as per regulatory guideline for the simultaneous quantitation of enasidenib and its active metabolite, AGI-16903 in mice plasma using an LC-MS/MS. Enasidenib and AGI-16903 along with internal standard were extracted from mice plasma using simple protein precipitation method. Chromatographic resolution of enasidenib, AGI-16903 and the internal standard (close analogue of AGI-16903) was achieved on a Chromolith RP-18e column using 0.2% formic acid:acetonitrile (15:85, v/v) as an eluent, which was delivered at a flow-rate of 1.2 mL/min. The MS/MS ion transitions monitored were m/z 474.1→267.2, 402.1→188.1 and 421.0→146.1 for enasidenib, AGI-16903 and the internal standard, respectively. The linearity range was 1.01–3023 ng/mL for both enasidenib and AGI-16903. The within-run and between-run accuracy and within-run and between-run precision were in the range of − 2.29 to 2.72 (as one value is in negative side). and 4.65–9.82%, respectively for enasidenib; 0.19–10.3 and 3.22–9.22%, respectively for AGI-16903. Both enasidenib and AGI-16903 were found to be stable in stability (up to three freeze-thaw cycles and for long-term at −80°C for 30 days) and processed (bench-top for 6 h and in in-injector for 24 h) samples. Application of the validated method was shown in a pharmacokinetic study in mice. |
| Databáze: | OpenAIRE |
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