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Assessing the Similarity between Random Copolymer Drug Glatiramer Acetate by Using LC-MS Data Coupling with
Hsin-Yi Wu1, Mi-Chia Ma2, Yu-Yi Pan2
1Instrumentation Center , National Taiwan University , Taipei 106 , Taiwan.
Analytical Chemistry
|October 9, 2019
Summary
A new hypothesis testing method using LC-MS analyzes glatiramer acetate (GA) drugs. This approach effectively evaluates similarity between drug lots and reference products, crucial for nonbiological complex drugs (NBCDs).
Area of Science:
- Analytical Chemistry
- Pharmaceutical Sciences
- Biochemistry
Background:
- Full characterization of nonbiological complex drugs (NBCDs) remains challenging.
- Analytical methods are essential for lot-to-lot consistency and comparison with reference products.
- Glatiramer acetate (GA) is an example of an NBCD requiring robust analytical evaluation.
Purpose of the Study:
- To develop and validate a hypothesis testing approach for assessing similarity between random amino acid copolymer drugs.
- To evaluate the similarity of different lots of glatiramer acetate (GA) and compare commercial products with synthesized versions.
- To establish a method for monitoring lot-to-lot variations in NBCDs.
Main Methods:
- Liquid chromatography-mass spectrometry (LC-MS) analysis after Lys-C digestion.
- HILIC-MS for separation and detection of drug-derived features.
- A sum of squared deviations hypothesis testing approach for high-dimensional LC-MS data.
Main Results:
- The hypothesis testing approach demonstrated significant similarity between Copaxone lots (ρ̂(95%) = 0.0056, p=0.0026) and between Copaxone and synthesized SPT (ρ̂ = 0.0026, p<0.0001).
- A clear lack of similarity was observed when comparing Copaxone to a negative control (ρ̂ = 0.036, p=1.00).
- Validation using stable isotope-labeled peptides confirmed sequence identification accuracy, with quantitation variations at 6.8-7.7%.
Conclusions:
- The proposed hypothesis testing approach is effective for evaluating similarity in NBCDs like glatiramer acetate.
- This method holds significant potential for comparing generic NBCDs with reference drugs and monitoring manufacturing consistency.
- The analytical strategy provides a valuable tool for quality control in the pharmaceutical industry.
