USP <467> Residual Solvents

[mennis]

The USP <467> states, “When the information about the presence of specific residual solvents is available, only Procedure C is needed to quantify the amount of residual solvents present.”

When testing by Procedure C for one particular solvent, in this case lets assume methanol, do you still inject the class 1 standard, Class 1 system suitability solution, and the Class 2 mixture A Standard Solution to verify resolution and s/n ratios?

I don’t understand why these solutions need to be injected during Procedure C if you are testing for a solvent that is not associated with these system suit requirements. The s/n of class 1’s and the resolution between Acetonitrile and Methylene chloride have nothing to do with the methanol being tested.

Just trying to get a feel for what everyone else out there is doing. I appreciate any viewpoints on this scenario.

[RhysB]

I am currently going through a validation process to test residual solvents in a finished product.
If you read through the fine print under the various solvent classes it says that you should follow the procedures listed in the 'instrument' section where posible. The next sentence reads 'Otherwise an appropriate validated proceedure is to be employed'.

As our manufacturing processes (purified animal extracts) only use methanol, ethanol and ethyl acetate, its completely pointless looking for the rest. We don't have a headspace unit (and the company doesn't have the money to purchase one any time soon) so all samples are disolved in DMSO (they will not go into water). The other problem is that the test methods are all about 60 minutes (give or take). Nice if you have the time, not good if people are hounding you for results. as the 3 solvents separate nicely I've stripped the method down to 20 minutes (and it could be less but I want to make sure I burn everything off the column).

So, for better or worse, I've taken the USP as a base and then modified it to suit my local working environment. Hope this helps you a bit.

Cheers,
Rhys

[krickos]

Hi

To answer the orginal question, yes it cleary states that you have to inject the SST solutions "Chromatograph the Class 1 Standard Solution, the Class 1 System Suitability Solution, and the Class 2 Mixture A Standard Solution, and record the peak responses as directed for Procedure: the signal-to-noise ratio of 1,1,1-trichloroethane in the Class 1 Standard Solution is not less than 5; the signal-to-noise ratio of each peak in the Class 1 System Suitability Solution is not less than 3; and the resolution, R, between acetonitrile and methylene chloride in the Class 2 Mixture A Standard Solution is not less than 1.0."

Why? Simply put because you use a generic pharmacopiea procedure and SSTs may not necessarily be related to your specific peaks of intrest.

As RhysB indicated you will in long term perspective usually gain on validating a faster procedure on your own, with SSTs based on solvents present in your specific manufacturing.

[DSP007]

Hello

It's a problem of non-specific (universal) metods.
As said china proverb and russian proverb :

It is hard to find a black cat in a dark room, where there is none in room (Kon-Fu-Czi 孔夫子 )

Unable to grasp the immensity [nelzja objat neobjatnoe]

What to do :
I guess we must proceed from the idea that it is necessary to control the quality and safety, and not perform a prescribed ritual, like the Papuans in cargo cult

Accordingly, the production is not necessary to look for something which is not, but must be prepared to document what it is you're right.

In general, search of ethanol "as a residual solvent" touches me.Especially when you consider how much of it in a drink of beer ...

In practice, only one case in my memory it was necessary to check the amount of isopropanol.

When the drug substance is passed to the "endocrine plant" in Moscow with an accuracy of 10 kg + / - 0.1 g on the act of reception and transmission.
And the evaporation of isopropanol through the package leads to friction between the plants.

For example, in the act of written
"Gross weight of 9.7623 kg" on the fact of 9.7603 kg. Who stole 2 grams of drugs?