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Published on: January 31, 2025
Solid-phase microextraction for assessment of plasma protein binding, a complement to rapid equilibrium dialysis
Sheelan Ahmad1,2, Daniel Baker2, Darragh Murnane2
1Research & Development, GlaxoSmithKline, Stevenage, UK.
Solid-phase microextraction (SPME) offers a reliable alternative for measuring plasma protein binding (PPB), crucial for drug development. SPME results closely align with the gold standard, rapid equilibrium dialysis (RED), ensuring accurate pharmacokinetic and pharmacodynamic assessments.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Biochemistry
Background:
- Plasma protein binding (PPB) is critical for understanding drug pharmacokinetics and pharmacodynamics.
- The free concentration of a drug determines its pharmacological activity.
- Accurate PPB measurement is vital for drug development and therapeutic efficacy.
Purpose of the Study:
- To investigate Solid-phase microextraction (SPME) as a method for determining plasma protein binding (PPB).
- To compare SPME's PPB measurements against the gold standard, rapid equilibrium dialysis (RED).
- To evaluate SPME as a potential alternative platform for PPB determination in biological matrices.
Main Methods:
- Solid-phase microextraction (SPME) technique was employed for PPB measurement.
- Comparison of SPME results with those obtained from rapid equilibrium dialysis (RED).
- Analysis of PPB for metoprolol, propranolol, and diclofenac across three concentrations.
Main Results:
- SPME-derived PPB values showed strong correlation with literature values.
- SPME results were comparable to those determined by RED.
- Average PPB percentages for metoprolol, propranolol, and diclofenac by SPME were 31.7%, 86.6%, and 99.0%, respectively, closely matching RED values.
Conclusions:
- SPME is a viable and accurate alternative method for determining plasma protein binding.
- The study provides evidence supporting SPME's utility in pharmacokinetic and pharmacodynamic assessments.
- SPME offers a promising platform for routine PPB determination in drug research.
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