residual solvents tfa

[scio2]

Hi, can anyone please point me in the direction of where to find information on justifying residual levels of class 4 solvents in pharmaceutical products.

Thanks in advance

scio

[chromatographer1]

Where do you find Class 4 solvents listed? The USP only has Class 1, 2, + 3. There is a table 4 but not Class 4.

Please clarify your request. Thanks.

Rod

[zokitano]

Where do you find Class 4 solvents listed? The USP only has Class 1, 2, + 3.

This is the same with the European Pharmacopoeia too.

[scio2]

Hi, yes, I am referring to solvents in Table 4: Substances for which no
adequate toxicological data were found. (a PDE can not be determined)

Sorry for the confusion

Scio

[chromatographer1]

These first five should be no problem using headspace for the means of analysis.

Isopropyl ether
Methyl isopropyl ketone
Methyltetrahydrofuran
hexane
Isooctane

These last five might pose difficulties. The first two should be done by IC in my opinion. The last three may have poor stability for prolonged heating in a headspace method and somewhat reactive. They should also be very volatile and easily partitioned.

Trichloroacetic acid
Trifluoroacetic acid
1,1-Dimethoxymethane
2,2-Dimethoxypropane
1,1-Diethoxypropane

While I have some experience with the first group I don't recommend headspace analysis for the second group.

Since the USP says there is no adequate toxicological data available I don't know how anyone could justify any levels of residual solvent. If one could demonstrate that a very low limit is not breached, that might be adequate to the regulatory authorities to approve the release of a product.

best wishes,

Rod

[scio2]

thanks rod!