Abstract
In our research, a straightforward UPLC-MS/MS method, with diazepam as the internal standard (IS), was proposed and acknowledged to determine the concentrations of enasidenib in rat plasma. When preparing the sample, we used acetonitrile for protein precipitation. The gradient elution method was used, and the mobile phase was acetonitrile and 0.1% formic acid. Diazepam was used as the IS. We used the Acquity UPLC BEH C18 column to separate enasidenib and IS. Under the positive ion electrospray ionization (ESI) source conditions, the mass transfer pairs of enasidenib were monitored by multiple reaction monitoring (MRM) to be m/z 474.2 ⟶ 456.1 and m/z 474.2 ⟶ 267.0, and the IS mass transfer pairs were m/z 285.0 ⟶ 154.0. Enasidenib had good linearity (r2 = 0.9985) in the concentration range of 1.0–1000 ng/mL. Besides, the values of intraday and interday precision were 2.25–8.40% and 3.94–5.46%, respectively, and the range of the accuracy values varied from −1.44 to 2.34%. Matrix effect, extraction recovery, and stability were compliant with FDA approval guidelines in terms of bioanalytical method validation. We had established a new method that had been applied to the pharmacokinetic study of enasidenib in rats.
Highlights
Acute myeloid leukaemia (AML) is a disease of bone marrow hematopoietic stem cells [1]
AML was typically characterized by the accumulation of immature myeloid cells in the bone marrow and inhibition of bone marrow hematopoiesis [2]. e clinical manifestations of AML were anemia, hemorrhage, infection, fever, organ of infiltration, and so on
Age, weight, race, mild liver damage, and kidney damage were thought to alter the pharmacokinetics of enasidenib [8,9,10]
Summary
Acute myeloid leukaemia (AML) is a disease of bone marrow hematopoietic stem cells [1]. E current main treatment strategies for AML include intensive chemotherapy, nonintensive chemotherapy, and small molecule inhibitors [4]. Enasidenib (Figure 1(a)) was a small molecule isocitrate dehydrogenase-2 (IDH2) inhibitor and was approved in the USA on 1 August 2017 for the treatment of patients with relapsed or refractory AML and IDH2 mutations [5, 6]. Enasidenib has provided a new treatment approach for patients with refractory AML with recurrence and IDH2 mutations [11,12,13]. It is believed that detecting enasidenib in plasma would help to establish the properties of pharmacokinetics and investigate the drug-drug interactions in animal models. This article, a quick, straightforward, and accurate UPLCMS/MS method was proposed and acknowledged to quantify enasidenib level and had been applied to the pharmacokinetic study of enasidenib
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