Chromatography Forum

Hi,

I am working on RP-HPLC method for a drug substance. The main peak area of the stock solution in MeOH was found stable in 24 hours. The assay result of the method showed good linearity, precision and accuracy. However, while I checked the impurity profile, a small decomposition peak appeared in the stock solution (probably produced by reaction with MeOH) and inceased to nearly 1% of the main peak area in 24 hour. Should I exclude MeOH as solvent for preparing stock solution? Moreover, could I still use MeOH for organic phase of MP?

Tons of thanks!

(1) Make up standard solution every day
(2) Evaluate whether refrigeration of the standard solution helps
(3) Since you're still in the experimentation phase would an alternative solvent like acetonitrile help, hurt, or no change?
(4) If you change to a different sample and standard solvent, could you still use methanol in the mobile phase - I'd say YES, as the analyte would only be in contact with methanol (in the column) for a few minutes, so any degradation would be miniscule