Validated HPLC-UV method for quantification of paxalisib, a pan PI3K and mTOR inhibitor in mouse plasma: Application to a pharmacokinetic study in mice.
Ashok ZakkulaHarsha K TripathyRama Murthi BesthaA B VinodVinay KiranSreekanth DittakaviRamesh MullangiPublished in: Biomedical chromatography : BMC (2023)
Paxalisib is a pan-PI3K and mTOR inhibitor, currently entering into Phase II clinical trials as a potential drug to treat glioblastoma patients. We report the development and validation of a high-performance liquid chromatography (HPLC) method for the quantitation of paxalisib in mouse plasma as per the US Food and Drug Administration regulatory guidelines. From the mouse plasma, paxalisib and the internal standard (IS; filgotinib) were extracted using ethyl acetate as an extraction solvent. The chromatographic separation of paxalisib and the IS was accomplished on a Symmetry C 18 (250 × 4.6 mm, 5.0 μm) column maintained at 40°C using 10 mm ammonium formate and acetonitrile in gradient conditions at a 0.8 ml/min flow-rate. The injection volume was 20 μl. The elution was monitored using a photo-diode array detector set at λ max 280 nm. Paxalisib and the IS eluted at 6.5 and 5.9 min, respectively with a total run time of 10 min. The calibration curve was linear over the range of 111-4,989 ng/ml. Inter- and intraday precision and accuracy, stability studies, dilution integrity and incurred sample reanalysis were investigated and the results met the acceptance criteria. The validated HPLC method was extended to assess the pharmacokinetic parameters of paxalisib in mice.
Keyphrases
- high performance liquid chromatography
- simultaneous determination
- liquid chromatography
- solid phase extraction
- tandem mass spectrometry
- liquid chromatography tandem mass spectrometry
- phase ii
- clinical trial
- mass spectrometry
- ms ms
- end stage renal disease
- gas chromatography
- chronic kidney disease
- open label
- ionic liquid
- drug administration
- newly diagnosed
- cell proliferation
- high fat diet induced
- peritoneal dialysis
- ejection fraction
- transcription factor
- type diabetes
- randomized controlled trial
- metabolic syndrome
- photodynamic therapy
- emergency department
- magnetic resonance imaging
- magnetic resonance
- prognostic factors
- high throughput
- drug induced
- study protocol
- ultrasound guided
- tyrosine kinase
- patient reported outcomes
- human health
- computed tomography
- adipose tissue
- electron transfer