High throughput screening of active pharmaceutical ingredients by UPLC

Area of Science:

• Analytical Chemistry
• Pharmaceutical Sciences
• Chromatography

Background:

• Traditional high-performance liquid chromatography (HPLC) method development for drug candidates is often time-consuming and involves extensive trial-and-error screening.
• The need for faster, more efficient screening methods is critical in early-stage drug development to accelerate timelines.

Purpose of the Study:

• To evaluate Ultra performance Liquid Chromatography (UPLC) as an efficient screening approach for drug candidate method development.
• To compare the selectivity and peak capacity of UPLC with conventional HPLC methods.
• To assess the feasibility of UPLC for early-stage drug development screening.

Main Methods:

• Screening of three stationary phases (C-18, phenyl, Shield RP 18) using UPLC with small particle size columns (1.7 µm).
• Evaluation of thirteen active pharmaceutical ingredients (APIs) using a standardized mobile-phase gradient.
• Comparison of UPLC selectivity and peak capacity against conventional HPLC methods.
• Confirmation of screened impurities using Liquid Chromatography-Mass Spectrometry (LC/MS).

Main Results:

• UPLC columns with 1.7 µm particles theoretically provide significantly higher plate counts (35,000) compared to conventional columns (5 µm).
• UPLC demonstrated comparable or superior selectivity to conventional HPLC methods for the screened APIs.
• Simple, high-efficiency UPLC gradients proved effective for screening numerous compounds.
• Peak capacity was notably higher with 1.7 µm particle columns compared to 5 µm columns.

Conclusions:

• UPLC is a feasible and productive alternative to conventional multiparametric chromatographic screening for early-stage drug development.
• The high efficiency and simplified gradient approach of UPLC accelerate method development for drug candidates.
• UPLC facilitates faster screening and method development, contributing to efficient early-stage drug discovery processes.