Analytical Quality by Design for Chiral Pharmaceuticals: A Robust HPLC Method for Upadacitinib Enantiomeric...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Chiral pharmaceutical purity is critical for patient safety and drug efficacy.
• Upadacitinib (UPA), a Janus kinase 1 (JAK-1) inhibitor, requires stringent quality control for rheumatoid arthritis treatment.

Purpose of the Study:

• To develop and validate a robust High-Performance Liquid Chromatography (HPLC) method for simultaneous quantification of Upadacitinib (UPA) and its enantiomeric impurity.
• To apply analytical quality by design (AQbD) principles for method optimization and ensure suitability for pharmaceutical formulations.

Main Methods:

• Utilized analytical quality by design (AQbD) for systematic optimization of chromatographic conditions.
• Employed a Chiralpak IG column with isocratic elution (n-hexane/ethanol, 70:30 v/v), flow rate of 1.8 mL/min, UV detection at 230 nm, and column temperature of 40°C.
• Validated the method using accuracy profiles and assessed greenness using BAGI and RGB12 algorithms.

Main Results:

• Successfully developed an optimized HPLC method for simultaneous UPA and enantiomeric impurity quantification.
• Method validation confirmed suitability for pharmaceutical analysis.
• Environmental impact and sustainability were evaluated, demonstrating a greener analytical approach.

Conclusions:

• The developed HPLC method, optimized via AQbD, provides a reliable and sustainable tool for ensuring UPA enantiomeric purity.
• This contributes to enhanced quality control, regulatory compliance, and safer rheumatoid arthritis therapies.
• The study highlights the importance of sustainable analytical practices in pharmaceutical manufacturing.