Limit of n-Hexane

[kalyanaraman]

Dear Everybody,

The limit of n-Hexane as per ICH is 290 ppm in the drug substances. Generally hexane is a fraction of various pentanes and heptanes. What are the various fractions I have to test when hexane is used as solvent in the process? Is it required to validate the method for all the hexane fractions?

Thanks

[chromatographer1]

You state:

Generally hexane is a fraction of various pentanes and heptanes.

I think you meant that hexane HAS a fraction of various pentanes and heptanes.

That is true, and the cheaper grades of hexane contain 5% or so of the impurities you mention, but there are grades that are >99%

If you are looking for a good std to measure hexane in a product matrix, use the same hexane solvent used in the matrix for the std.

The other option is simply to use a very short capillary column or a normal length packed column to measure the hexane. That way if any small impurities ARE present they will coelute with the main peak hexane and be measured as one peak. The respond factors of hexane and its impurities on a FID are not different enough to be of concern. We are talking of less than 1%. Even if the main peak in 'the hexane' is actually 2-methyl pentane its response @ 290 ppm will correspond to the true hexane response of 287 ppm. Since the impurities of hexane are generally only at a maximum of 5%, we are talking about 5% of 3 ppm difference ! Not enough difference to worry about, right?

Hope my comments are helpful.

[Carlos Teixeira]

Hello Dears Friends,

I had this same problem. I did it:

1 - I used n-Hexane at 99.5% from Merck (Germany) - but You can use another brand, Ok?!
This n-Hexane has small peaks relative to Hexane isomers.

2 - With this n-Hexane as my Working Standard I did perform the assay of my Hexane (industrial grade - because our manufactury process used it) and by the difference my Hexane-isomers.

3 - I considered than my limit of 290ppm were the somatory of all Hexane (so chromatographic purity = area from all Hexane peaks) and could stablish the limit for all Hexane isomers.


Have good elutions!!!

Carlos Teixeira