Rapid LC-MS/MS Bosutinib Quantification with Applications in Metabolic Stability Estimation

Bosutinib (BOS) is FDA approved drug for the treatment of chronic phase (CP) Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). We report a fast, sensitive, and simple LC-MS/MS method, validated for the determination of BOS in human liver microsomes, utilizing tofacitinib (TO...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-02, Vol.28 (4), p.1641
Main Authors: Attwa, Mohamed W, Alanazi, Mohammed M
Format: Article
Language:English
Subjects:
Accuracy
Acetonitrile
Aniline Compounds
Bosutinib
Calibration
Chemical properties
Chromatography
Chromatography, Liquid - methods
Chronic myeloid leukemia
Diarrhea
Drug metabolism
Drug Stability
Drugs
Flow velocity
Formic acid
Humans
in vitro half-life
intrinsic clearance
Ionization
Leukemia
Liquid chromatography
Liver
Mass spectrometry
Measurement
metabolic stability
Metabolism
Methods
Microsomes
Mutation
Nitriles
Pharmaceutical research
Philadelphia chromosome
Physiological aspects
Positive ions
Proteins
Quadrupoles
rapid LC-MS/MS
Reproducibility of Results
Room temperature
Stability analysis
Tandem Mass Spectrometry - methods
Targeted cancer therapy
validation
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Summary:Bosutinib (BOS) is FDA approved drug for the treatment of chronic phase (CP) Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). We report a fast, sensitive, and simple LC-MS/MS method, validated for the determination of BOS in human liver microsomes, utilizing tofacitinib (TOF) as the internal standard. The separation of BOS and TOF was done using a 1.8 μm C18 column (2.1 × 50 mm) at room temperature using the isocratic elution system of acetonitrile-water (30:70, / ) containing 0.1 M formic acid at a flow rate of 0.15 mL/min, and a triple-quadrupole tandem mass spectrometer (TQD-MS) with an electrospray ionization (ESI) source that was operated in the positive ion mode. The method was validated according to the European Medicines Agency, and the rapid and specific quantification of BOS in human liver microsomes was achieved in the range of 5-200 ng/mL, with a determination coefficient of 0.999. Intra- and inter-day accuracy and precision values were
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28041641