Chromatography Forum

does anyone know how to separate 4-aminophenol from paracetamol using RP HPLC?

Thanks a lot, Tom.

This is a quick reply.

Does this mean any typical RP column with ion exchange mechanism will not provide good retention for 4-aminophenol?

Is the mix-mode column robust and reproducible from batch to batch, and well acceptable to FDA?

I am grateful.
Jim

Hi

The Ph. Eur. has a method. The resolution requirements between 4-aminophenol (Imp K) and Paracetamol is NLT 4.0. This application should provide a good starting point.

Regards
Mike

Thanks Mike.

USP has a SCX method but I am searching a RP method. I do not have easy access to Ph Eu. Do you notice the separation mode of the Ph Eu method?

Thanks
Jim

Hello.
Register at Pharmeuropa online and get public draft of Pharmeuropa 28.1 that provides paracetamol too: https://extranet.edqm.eu/4DLink1/4DCGI/Web_View/mono/49

Does this mean any typical RP column with ion exchange mechanism will not provide good retention for 4-aminophenol?

Depends on the pH. The pKa's are listed as 5.5 and 10.5

Is the mix-mode column robust and reproducible from batch to batch, and well acceptable to FDA?

I don't have any hands-on experience with it, but it's been around for a while. I don't see how the FDA could have any objection so long as you do a proper validation.

Hi ym3142

I could email you the monograph. Please forward me your email address.

Regards
Mike

Thanks Mike

yingqunmao@gmail.com

Hi Mike

Thanks a lot for taking time sending me the Eu Ph.

I notice the Rt for 4-aminophenol was ~1.4 min and the void time is 1.6 min. K'<0.

What's the industry general practice and/or regulation requirements now? I thought K' should be >1.

Hi ym3142

This is not ideal as generally you would want k' to be at least 1. One way of increasing k' is by reducing the column temp i.e. from 35C to 25C. The organic portion of the mobile phase could also be reduced. This will have an impact on all the imps.

The USP 40 NF35 S2 has a method for 4-aminophenol in Acetaminophen API monograph. This method is a gradient method which will probably allow 4-aminophenol to be seperated from the void.


Regards

Hi Mike

Thanks again.

USP method is of SCX, which should be good for 4-aminophenol itself but I am afraid of it is no good for the separation of many other impurities I need to deal.