Protein kinase inhibitor analysis with the core-shell separation technique.

Area of Science:

• Analytical Chemistry
• Chromatography
• Pharmaceutical Analysis

Background:

• Protein kinase inhibitors are crucial in cancer therapy.
• Accurate and sensitive analysis of these inhibitors is essential for drug development.
• Existing analytical methods may have limitations in sensitivity and efficiency.

Purpose of the Study:

• To evaluate the application of core-shell separation technology for protein kinase inhibitor analysis.
• To compare the performance of core-shell columns with conventional columns in HPLC-DAD.
• To assess the cost-effectiveness and sensitivity improvements offered by this technology.

Main Methods:

• Utilized a Kinetex 2.6 μm C8 100 Å core-shell HPLC column for separation.
• Employed a mobile phase of 0.05 M H(3)PO(4)/KH(2)PO(4) (pH = 2.3)-acetonitrile (7:3, v/v) at 0.7 mL/min.
• Performed sample preparation using liquid-liquid extraction with 1-chlorobutane.

Main Results:

• Achieved good linearity (5-10,000 ng/mL) and a limit of quantification (LOQ) of 5 ng/mL for canertinib.
• Core-shell columns produced 2-3 times narrower and higher peaks compared to conventional columns.
• Recoveries ranged from 74-79%, with relative standard deviation and accuracy below 15%.

Conclusions:

• Core-shell separation technology offers a cost-effective enhancement for HPLC-based protein kinase inhibitor analysis.
• This approach significantly improves peak characteristics and sensitivity, approaching LC-MS/MS performance.
• The validated method demonstrates suitability for the precise quantification of protein kinase inhibitors.