Ibuprofen STD crashing out of solution 20% MeOH

[charlesvb]

My standard prep is 20% HPLC grade MeOH/ 80% HPLC water. The ibuprofen STD (purity 100%) is added to the MeOH and sonicated until dissolved. Then it is diluted to volume with water, and then re-diluted as it cools to room temp. It is 0.00776 M solution so I do not understand what could cause it to crash out. It happens slowly over a period of about 2-3 hours and only happens about 1/3 of the time. The pH of the prep is around 6. Any ideas??

[Consumer Products Guy]

Disclaimer: I've never worked with ibuprofen.

Ibuprofen is only slightly soluble in water itself (<1 mg/mL), more soluble when organic solvents are added. From its structure, if I was trying to keep ibuprofen in solution, I'd raise the pH as ibuprofen is a carboxylic acid and the ionized form would be more water soluble, or increase the methanol percentage.

However, is this a validated test method ? If so, you're stuck, must follow the test method as written. This kind of stuff should've become apparent during validation studies. I think I'd experiment as I suggested, then do some type of validation and make the change, because it sounds like the way you're doing it now is not too robust.