An Integrated Quality by Design RP-UPLC Method for Lumacaftor and Ivacaftor in Human Plasma

Area of Science:

• Analytical Chemistry
• Pharmacology
• Biomedical Science

Background:

• Cystic fibrosis (CF) is a genetic disorder caused by CFTR gene mutations.
• Combination therapy with ivacaftor (IVA) and lumacaftor (LUMA) is a common treatment for CF.
• Accurate quantification of IVA and LUMA in human plasma is crucial for effective therapeutic drug monitoring.

Purpose of the Study:

• To develop and validate a Quality by Design (QbD)-based Reversed-Phase Ultra-Performance Liquid Chromatography (RP-UPLC) method.
• To achieve simultaneous estimation of IVA and LUMA in human plasma.
• To ensure efficient separation from plasma interferences, reduce run time, and maintain consistent analytical performance.

Main Methods:

• Utilized a Waters Acquity UPLC system with a CSH C18 column.
• Optimized the method using a Central Composite Design model.
• Employed a mobile phase of 0.01 N ammonium acetate and acetonitrile (60:40, v/v) at 0.3 mL/min, with column temperature at 30°C.
• Used EMT as the internal standard and detected analytes at 260 nm.

Main Results:

• Achieved retention times of 1.45 min for EMT, 1.77 min for IVA, and 1.99 min for LUMA.
• The developed method demonstrated high reliability, rapidity, and selectivity.
• Exhibited excellent linearity, precision, and accuracy, meeting USFDA guidelines.

Conclusions:

• The QbD-based RP-UPLC method provides a robust and efficient analytical tool for quantifying IVA and LUMA in human plasma.
• This validated method supports accurate therapeutic drug monitoring for cystic fibrosis patients.
• The method's speed and accuracy contribute to optimized combination therapy management.