Analysis of formaldehyde in a injectable formulation

[Pegry]

Hi everybody,

we have to analyze the contents of formaldehyde in a injectable formulation. The product can contain up to 5% of formaldehyde. The formaldehyde is an hydrolysis product of the active compound.
The active is dissolved in water and after dissolution it produce an impurity and formaldehyde.
At acidic pH the rate of formation of formaldehyde increase but at basic pH the rate decrease.
We have searched for some methods of analysis of formaldehyde but the major part of the derivatization work in acidic media..
We have the problem to analyze the content of formaldehyde in the product and we need conditions that doesn't produce formaldehyde.
We have tried to derivatize formaldehyde with PFBHA and quantify it with HS-GC but we are not sure that we aren't creating formaldehyde..

Do you have some experience with analysis of aldehydes?
Do you have some cue to our problem?

Thanks in advance for the answer,

Have a good day!

[AICMM]

You can analyze formaldehyde directly without pre-derivatization. There are at least two ways I have seen it done. First is to use an FID with a methanizer that will convert the formaldehyde to methane which is then detectable by FID. Second is to use argon ionization detector which will ionized the formaldehyde (IP 10.9 eV) Both of these have been done by a fellow chemist I work with so I will try to find out more about columns and conditions.

Would probably work well in headspace mode but I cannot say that for sure.

[Pegry]

AICMM, thanks for the answer..

Unfortunately we don't have access to neither a methanizer or an argon ionization detector.. We have access to a GCMS that could detect formaldehyde as well..
Which column do you use to separate the formaldehyde? Do you get a good peak shape without derivatization?
Another problem with the sample is that we can't heat too much beacuse otherwise we will produce formaldehyde by degradation of the active compound..
I was thinking to dissolve the sample in DMSO to get a slower hydrolysis and derivatize with PFBHA (buffered at ph7 with phosphate), then make an headspace analysis at 30°C..

Do you have any suggestion?
Someone know any other approach to solve this?

Thanks in advance,

Bye

[AICMM]

Pegry,

Methanizer is a relatively inexpensive installation on standard GC's. However, I also Yahoo searched PFBHA and headspace and in the first page I found at least two articles that speak to the process you are interested in, including one ( Journal of Chromatography A, Vol. 1104, No. 1, pages 1-10 (2006)) that is directly related to what you want to do. In short, it looks doable.

I was going to get you column information from a friend of mine but if you are going to use PFBHA the column chosen would no longer be applicable.

On Yahoo, they also noted a method using a PFBHA coated SPME fiber which would also do the trick.

Good luck and best regards.