Chromatographic method development using multivariate approaches for organic solvents optimized analysis in...

Area of Science:

• Analytical Chemistry
• Radiopharmaceutical Chemistry

Background:

• [18F]fluorocholine is a critical radiopharmaceutical.
• Ensuring the purity of [18F]fluorocholine requires accurate quantification of organic solvent impurities.
• Existing methods may be time-consuming or require extensive sample preparation.

Purpose of the Study:

• To develop and validate a rapid, simple, and accurate analytical method for determining specific organic solvents in [18F]fluorocholine.
• To optimize method parameters using statistical design techniques.
• To implement the method for routine quality control of manufactured [18F]fluorocholine.

Main Methods:

• Gas Chromatography coupled with Flame Ionization Detection (GC-FID).
• Optimization using fractional factorial design, Doehlert design, and Desirability function.
• Method validation including recovery, repeatability, linearity, limit of detection, and limit of quantification.

Main Results:

• The method accurately quantifies ethanol, acetonitrile, dibromomethane, dimethylaminoethanol, and dimethyl sulfoxide.
• Validation demonstrated good recovery (85.1-104.1%) and repeatability (RSD ≤8.1%).
• Excellent linearity (R ≥ 0.983) and satisfactory detection/quantification limits (≤2.5 ppm / ≤7.5 ppm) were achieved.

Conclusions:

• The developed GC-FID method is fast, simple, and requires minimal manual operation and no sample preparation.
• It is suitable for routine analysis of organic solvents in [18F]fluorocholine, supporting monograph modernization.
• The method was successfully applied to assess manufactured [18F]fluorocholine samples at CDTN.