By Anonymous on Tuesday, May 20, 2003 - 09:20 am:
I'm interested in any information regarding quenching oxidation during forced degradation studies. I'm told that adding sodium metabisulfite can help but haven't found any literature on the topic.
Some folks I've spoken to make up their entire solution in the set concentration of hydrogen peroxide and aliquot out at exact time points without quenching and run their HPLC method. Others add a certain amount (say 5 mL 1% peroxide to 10 mg of compound) and bring up to a final volume at the predetermined time point and then immediately analyze by HPLC.
Anybody out there quenching prior to HPLC?
I'm trying to determine a consensus for what people are doing - any comments would be greatly appreciated!
By A.Nonymous on Tuesday, May 20, 2003 - 12:19 pm:
At my company it's just trial and error.
For some compounds, its nearly impossible to get soms oxidation degradant, so then you take the amount, add peroxide (sometimes heat) and after the time, bring up to volume.
Other compounds react heavily with peroxide, then you can dilute first, and then add some peroxide.
The first way you describe is sometimes usefull, because the reaction can be performed into a vial, wich can be injected with a time interval.
You can degradate over night, and choose the best time to continue with.
We always try to get a degradation of 10-20%, so you can quantitate your API at min 80%. If its getting lesser you have too much possibility for secondary degradation.
By Carlos Teixeira on Tuesday, May 20, 2003 - 02:48 pm:
Hi Anon 09:20
0 - Consider that the concentration for analysis of your APT is 0.01 mg/mL
1 - Dissolve your API in Methanol at high concentration, Ex. 0.5 mg/mL
2 - Dilute 5.0 mL of the solution 1 to 25 mL of Hydrogen Peroxide R (or 10% in MeOH). It is your reactional solution by Oxidative Process
This solution must be analysed at 0 hour (immediatelly), 1 hour and 24hours.
3 - Analyse the solution 2:
3.1 - Dilute 10.0mL of the solution 2 to 100 mL of Diluent.
3.2 - Preper a Blank solution.
You can to use reflux with the Solution 2 (by oh,1h and 24h).
By Tom Mizukami on Wednesday, May 21, 2003 - 08:27 am:
Sodium metabisulfite or sodium sulfite will quench the reaction. I don't have a real reference but I recalled from the MSDS http://www.sefsc.noaa.gov/HTMLdocs/HydrogenPeroxide30.htm see section 6.
Some people are very sensitive to exposure to very small amounts of sulfites. Another option might be the catalytic decomposition with MnO2, manganese(IV) oxide.
Although we try to neutralize the acid and base degradation samples, we don't try and stop the oxidation in sample with h2o2.