Development of a novel and quick UPLC-MS/MS method for the pharmacokinetic analysis of duvelisib in beagle dogs
| Autor: | Huidan Zhu, Saili Xie, Xiaoxiang Du, Ren-ai Xu, Yuanyuan Shao |
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| Rok vydání: | 2020 |
| Předmět: |
Analyte
Spectrometry Mass Electrospray Ionization Clinical Biochemistry Pharmaceutical Science Administration Oral Mass spectrometry 01 natural sciences High-performance liquid chromatography Analytical Chemistry chemistry.chemical_compound Dogs Liquid chromatography–mass spectrometry Limit of Detection Tandem Mass Spectrometry Drug Discovery Protein precipitation Animals Spectroscopy Chromatography High Pressure Liquid Phosphoinositide-3 Kinase Inhibitors Chromatography 010405 organic chemistry Chemistry 010401 analytical chemistry Selected reaction monitoring Reproducibility of Results Isoquinolines Duvelisib 0104 chemical sciences Triple quadrupole mass spectrometer Purines Calibration |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 187 |
| ISSN: | 1873-264X |
| Popis: | Duvelisib, a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor, was recently approved in the USA as the therapeutic drug for patients with the diseases of relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In the present study of our research, a quick and simple bioanalytical method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was fully explored and established for the quantification of plasma duvelisib concentrations from beagle dog in which gilteritinib was used as the internal standard (IS). After a simple and quick protein precipitation treated with acetonitrile, the chromatographic separation of the analyte was carried out on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) conducted in a gradient elution procedure where acetonitrile (solvent A) and 0.1 % formic acid in water (solvent B) consisted as the mobile phase. The measurements of the analyte and IS were explored using a XEVO TQS triple quadrupole tandem mass spectrometer, which was comprised with electrospray ionization (ESI) source in positive ion mode. Selected reaction monitoring (SRM) mode was employed to detect the parent-to-daughter ion transitions as follows: m/z 416.88 → 281.88 for duvelisib, and m/z 553.09 → 436.01 for IS, respectively. The assay was successfully established in the calibration range from 0.5 to 3000 ng/mL for duvelisib, where the lower limit of quantification (LLOQ) was set at 0.5 ng/mL. The precisions of intra-day and inter-day for duvelisib were all below 12.6 %, and the accuracies were from -2.5% to 14.1%. Both matrix effect and mean recovery of the analyte and IS were all acceptable, and the analyte was stable during the assay and storage in dog plasma samples. The novel established bioanalytical method based on UPLC-MS/MS technique was effectively employed to the investigation of the pharmacokinetic profile of duvelisib in beagle dogs following a 1.34 mg/kg single dose of oral administration. |
| Databáze: | OpenAIRE |
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