Stress conditions in pharmaceutical products

[Tequila]

Dear members of this forum,

I need to start with stress conditions studies and I would like to know any important points in order not to damage the C18 column.
I have to work with hydrolytic conditions with HCl 1 N and NaOH 1 N and reflux for about 30 minutes. It is important to neutralize the solutions before the injection.
I have to work with oxidative condition amd H2O2 3 % and reflux for about 30 minutes. In this study I do not have to take any aditional step because the H2O2 is not more in solution owing to the high temperatures.
I would like if these points is a good way to start to work or is important to do any changes to start the stress conditions work.
Thanks in advance for your help,

Diego

[Rob Burgess]

It would be prudent to neutralize your degradation samples prior to injection to stop any further degradation inside your vials while awaiting injection.

[DR]

You can also expose samples to heat (without acid, base or peroxide) and light. The trick is to not go too far. If your treated samples drop their main peak areas by ~10%, you've degraded them (more than) enough. It usually takes some playing with exposure times and/or acid/base/peroxide concentrations to get somewhere between "no effect" and "total annihilation".

[gtma]

I not sure why you would want to use 1N HCl or 1N NaOH. I'm guessing your drug substance is relatively stable in 0.1N HCl or NaOH or it takes too long to achieve 5-20% degradation in these conditions. Anyway, depending on your injection volume and column dimension, you may be okay to inject 1N solution without affecting your column. I usually don't have a problem injection 10 ul of 0.1N acid or base solution on a 4.6 X 150 mm column. Based on my experience, I usually quench the peroxide solution more frequently than neutralize the acid/base solutions. As "DR" suggested, you need to play around with the conc and exposure time. My suggestion is to program the HPLC to inject the acid, base, peroxide - drug solutions (prep at different conc) at predetermined interval (e.g. 1, 4, 8, 12, 24 hrs, etc) and evaluate the results to derive the best conc and exposure time.

Please see the following discussion link for further discussion on this topic: "Forced Degradation in the drug products". Please provide feedback on how it went.

[DR]

Yes, I like the sound of this approach - just inject regularly and take the one that shows ~10% (for example) drop for each condition. With some autosamplers, you could even automate subsequent additions of acid & base to allow for automated reaction & quenching or replicates...

[michaelcarolus]

Hi Diego

If you interested I have an article on stress testing/forced degradation.

Cheers
Mike

[Tequila]

Dear Mike,

I am interested in any articles about this subject because all is new for me and I try not to damage my columns when I have to work with experiments works.
Thanks in advance for your help,

Diego
E-mail: tequila2@adinet.com.uy

[Tequila]

Dear Mike,

I am interested in any articles about this subject because all is new for me and I try not to damage my columns when I have to work with experiments works.
Thanks in advance for your help,

Diego
E-mail: tequila2@adinet.com.uy

[Tequila]

Dear Mike,

I am interested in any articles about this subject because all is new for me and I try not to damage my columns when I have to work with experiments works.
Thanks in advance for your help,

Diego
E-mail: tequila2@adinet.com.uy

[salfar]

Dear Mike,

I am also interested in those articles you have concerning stress degradation studies. Could you send them to salfar@bluepharma.pt?

Best regards,

Sonia

[yaoguocan]

Dear Mike,

I am also interested in those articles you have concerning stress degradation studies. I doubt my samples degradate due to high stress Could you send them to yaoguocan@163.com?

Best regards,

Guocan Yao